Intravenous pentoxifylline does not affect the exercise-induced pulmonary arterial, capillary or venous hypertension in Thoroughbred horses

The present study was carried out to examine whether intravenously administered pentoxifylline-a phosphodiesterase inhibitor which increases red blood cell deformability and decreases blood viscosity-would attenuate the magnitude of exercise-induced pulmonary capillary hypertension in healthy, fit Thoroughbred horses and in turn, diminish the occurrence of exercise-induced pulmonary hemorrhage (EIPH). Experiments were carried out on six healthy, sound, exercise-trained Thoroughbred horses. Hemodynamic data were collected at rest, and during exercise performed at 8 and 14 m/sec on 3.5% uphill grade in the control (no medications) and the pentoxifylline (8.5 mg/kg, i.v.) experiments. The sequence of treatments was randomized for every horse and 7 days were allowed between treatments. Galloping at 14 m/sec on 3.5% uphill grade elicited maximal heart rate. In both treatments, simultaneous measurements of phasic and mean right atrial and pulmonary arterial, capillary and wedge pressures were made using catheter-tip-manometers whose signals were carefully referenced at the point of the left shoulder. In the control study, exercise resulted in progressive significant increments in heart rate, right atrial and pulmonary arterial, capillary and venous pressures; thereby, confirming that exercising Thoroughbreds develop significant pulmonary hypertension. All horses experienced exercise-induced pulmonary hemorrhage (EIPH) in the control experiments. Pentoxifylline administration to standing horses caused anxiety, tachycardia, muscular fasciculations/tremors and mild sweating, but statistically significant changes in right atrial and pulmonary arterial, capillary and venous pressures were not detected. Exercise in the pentoxifylline treatment also resulted in progressive significant increments in heart rate and right atrial as well as pulmonary vascular pressures, but these data were not statistically significantly different from those in the control study and the incidence of EIPH remained unchanged. Thus, it was concluded that i.v. pentoxifylline is ineffective in attenuating the exercise-induced pulmonary arterial, capillary and venous hypertension in healthy, fit Thoroughbred horses.     

Pulmonary vascular pressures of thoroughbred horses exercised 1, 2, 3 and 4 h after furosemide administration

Furosemide premedication of horses 4 h prior to exercise significantly attenuates exercise-induced pulmonary capillary hypertension which may help diminish the severity of exercise-induced pulmonary haemorrhage. As pulmonary hemodynamic effects of furosemide may be mediated via a reduction in plasma volume (which is most pronounced 15-30 min postfurosemide administration, with plasma volume recovering thereafter), we hypothesized that administration of furosemide at intervals shorter than 4 h before exertion may be more effective in attenuating the exercise-induced rise in pulmonary capillary blood pressure. Thus, our objective was to determine whether furosemide-induced attenuation of exercise-induced pulmonary arterial, capillary and venous hypertension would be enhanced when the drug is administered at intervals shorter than 4 h before exercise. Using established techniques, right atrial, and pulmonary arterial, capillary and wedge (venous) pressures were ascertained in seven healthy, sound, exercise-trained Thoroughbred horses in a randomized split-plot experimental design. Measurements were made at rest and during exercise performed at maximal heart rate (217 +/- 3 beats/min) in the control (no medications) experiments and following furosemide administration (250 mg intravenously (i.v.)) at 1, 2, 3 and 4 h before exercise. Sequence of treatments was randomized and 7 days were allowed between experiments on each horse. Although furosemide administration in the four treatment groups caused only insignificant changes in the pulmonary arterial, capillary and wedge pressures of standing horses, furosemide-induced reduction in mean right atrial pressure achieved statistical significance in the 2 h postfurosemide experiments. In the control studies, exercise was attended by statistically significant increments in mean right atrial, as well as pulmonary arterial, capillary and wedge pressures. Although exercise in each of the four furosemide experiments was also attended by significant increments in right atrial as well as pulmonary vascular pressures, in the 1, 2 and 3 h postfurosemide experiments, mean right atrial pressure increased to a significantly lower value than in the control study. Exercise-induced changes in pulmonary vascular pressures in the 1 h postfurosemide experiments were not different from the pressures in the control study. There was a significant attenuation of exercise-induced pulmonary capillary and venous hypertension in the 2, 3 and 4 h postfurosemide experiments, but significant differences among these treatments were not found. Thus, these data did not support the contention that administration of furosemide at intervals shorter than 4 h before exercise is more effective in attenuating exercise-induced pulmonary capillary or venous hypertension in Thoroughbred horses.     

Clenbuterol administration does not enhance the efficacy of furosemide in attenuating the exercise-induced pulmonary capillary hypertension in Thoroughbred horses

The stimulation of pulmonary beta2-adrenergic receptors causes a decrease in vascular resistance. Thus, the present study was carried out to examine whether concomitant administration of clenbuterol-a beta2-adrenergic receptor agonist, to horses premedicated with furosemide would attenuate the exercise-induced pulmonary capillary hypertension to a greater extent than furosemide alone, and in turn, affect the occurrence of exercise-induced pulmonary hemorrhage (EIPH). Experiments were carried out on six healthy, sound, exercise-trained Thoroughbred horses. All horses were studied in the control (no medications), furosemide (250 mg i.v., 4 h pre-exercise)-control, and furosemide (250 mg i.v., 4 h pre-exercise)+clenbuterol (0.8 microg/kg i.v., 11 min pre-exercise) experiments. The sequence of these treatments was randomized for every horse, and 7 days were allowed between them. Using catheter-tip-transducers whose in-vivo signals were referenced at the point of the left shoulder, pulmonary vascular pressures were determined at rest, sub-maximal exercise, and during galloping at 14.2 m/s on a 3.5% uphill grade--a workload that elicited maximal heart rate. In the control study, incremental exercise resulted in progressive significant (P<0.05) increments in heart rate, right atrial as well as pulmonary arterial, capillary and venous (wedge) pressures, and all horses experienced EIPH. Furosemide administration caused a significant (P<0.05) reduction in mean right atrial as well as pulmonary capillary and venous pressures of standing horses. Although exercise in the furosemide-control experiments also caused right atrial and pulmonary vascular pressures to increase significantly (P<0.05), the increment in mean pulmonary capillary and wedge pressures was significantly (P<0.05) attenuated in comparison with the control study, but all horses experienced EIPH. Clenbuterol administration to standing horses premedicated with furosemide caused tachycardia, but significant changes in right atrial or pulmonary vascular pressures were not discerned at rest. During exercise in the furosemide+clenbuterol experiments, heart rate, mean right atrial as well as pulmonary arterial, capillary and wedge pressures increased significantly (P<0.05), but these data were not different from the furosemide-control experiments, and all horses experienced EIPH as well. Thus, it was concluded that clenbuterol administration is ineffective in modifying the pulmonary hemodynamic effects of furosemide in standing or exercising horses. Because the intravascular force exerted onto the blood-gas barrier of horses premedicated with furosemide remained unaffected by clenbuterol administration, it is believed that concomitant clenbuterol administration is unlikely to offer additional benefit to healthy horses experiencing EIPH.     

Clenbuterol administration does not attenuate the exercise-induced pulmonary arterial, capillary or venous hypertension in strenuously exercising Thoroughbred horses

The present study was carried out to ascertain whether beta2-adrenergic receptor stimulation with clenbuterol would attenuate the pulmonary arterial, capillary and venous hypertension in horses performing high-intensity exercise and, in turn, modify the occurrence of exercise-induced pulmonary haemorrhage (EIPH). Experiments were carried out on 6 healthy, sound, exercise-trained Thoroughbred horses. All horses were studied in the control (no medications) and the clenbuterol (0.8 pg/kg bwt, i.v.) treatments. The sequence of these treatments was randomised for every horse, and 7 days were allowed between them. Using catheter-tip-transducers whose in-vivo signals were referenced at the point of the left shoulder, right heart/pulmonary vascular pressures were determined at rest, sub-maximal exercise and during galloping at 14.2 m/s on a 3.5% uphill grade--a workload that elicited maximal heart rate and induced EIPH in all horses. In the control experiments, incremental exercise resulted in progressive significant increments in right atrial as well as pulmonary arterial, capillary and venous (wedge) pressures and all horses experienced EIPH. Clenbuterol administration to standing horses caused tachycardia, but significant changes in mean right atrial or pulmonary vascular pressures were not observed. During exercise performed after clenbuterol administration, heart rate as well as right atrial and pulmonary arterial, capillary and wedge pressures also increased progressively with increasing work intensity. However, these values were not found to be statistically significantly different from corresponding data in the control study and the incidence of EIPH remained unaffected. Since clenbuterol administration also does not affect the transpulmonary pressure during exercise, it is unlikely that the transmural force exerted onto the blood-gas barrier of exercising horses is altered following i.v. clenbuterol administration at the recommended dosage.     

Intravenous pentoxifylline does not enhance the pulmonary haemodynamic efficacy of frusemide in strenuously exercising thoroughbred horses

The present study was carried out to examine whether pentoxifylline administration to horses premedicated with frusemide would attenuate the exercise-induced pulmonary arterial, capillary and venous hypertension to a greater extent than frusemide alone, thereby affecting the occurrence of exercise-induced pulmonary haemorrhage (EIPH). Using established techniques, we determined right heart and pulmonary vascular pressures in 6 healthy, sound Thoroughbred horses at rest and during exercise performed at maximal heart rate at a workload of 14 m/s on 3.5% uphill grade in the control (no medications), frusemide (250 mg i.v., 4 h pre-exercise)-control, and the frusemide (250 mg i.v., 4 h pre-exercise) + pentoxifylline (8.5 mg/kg bwt i.v., 15 min preexercise) treatments. Sequence of the 3 treatments was randomised for every horse and 7 days were allowed between them. In the control study, galloping at 14 m/s on 3.5% uphill grade elicited significant right atrial as well as pulmonary arterial, capillary and venous hypertension and all horses experienced EIPH as detected by the presence of fresh blood in the trachea on endoscopic examination. Frusemide administration was not attended by changes in heart rate at rest or during exercise. Although in the frusemide-control experiments, a significant reduction in mean pulmonary arterial, capillary and wedge pressures was observed both at rest and during galloping at 14 m/s on 3.5% uphill grade, all horses still experienced EIPH. Pentoxifylline administration to standing horses premedicated with frusemide caused nervousness, muscular fasciculations, sweating and tachycardia. Although these symptoms had largely abated within 15 min, there were no significant changes in the right atrial or pulmonary vascular pressures. Exercise in the frusemide + pentoxifylline experiments also caused significant right atrial as well as pulmonary arterial, capillary and venous hypertension, but these data were not found to be significantly different from the frusemide-control experiments. All horses in the frusemide + pentoxifylline experiments also experienced EIPH. In conclusion, our data indicate that pentoxifylline (8.5 mg/kg bwt i.v., 15 min pre-exercise) is ineffective in modifying the pulmonary haemodynamic effects of frusemide in exercising horses. It should be noted, however, that we did not examine whether erythrocyte plasticity was altered by the administration of pentoxifylline. Since the intravascular force exerted onto the blood-gas barrier of exercising horses premedicated with frusemide remained unaffected by pentoxifylline administration, it is concluded that concomitant pentoxifylline administration is unlikely to offer additional benefit to horses experiencing EIPH.     

Pulmonary vascular pressures of strenuously exercising Thoroughbreds after administration of varying doses of frusemide

The frusemide dose-response for attenuation of exercise-induced pulmonary capillary hypertension was studied in 7 healthy, exercise-conditioned Thoroughbred horses using previously described haemodynamic procedures. Four different doses of frusemide were tested: 250 mg regardless of bodyweight (amounting to 0.56 +/- 0.03 mg/kg bwt), 1.0 mg/kg bwt, 1.5 mg/kg bwt and 2.0 mg/kg bwt. Frusemide was administered i.v., 4 h before exercise. Haemodynamic data were obtained at rest and during treadmill exercise performed at 14.2 m/s on a 3.5% uphill grade; this workload elicited maximal heart rate of horses. Airway endoscopy was performed post exercise to detect exercise-induced pulmonary haemorrhage (EIPH). In standing horses, frusemide administration resulted in a significant (P<0.05) decrease in mean pulmonary arterial, pulmonary capillary and pulmonary artery wedge pressures, but significant differences among the various frusemide doses were not observed. In the control experiments, exercise caused significant increments in the right atrial as well as pulmonary arterial, wedge, and capillary pressures, and all horses experienced EIPH. Following frusemide administration, the exercise-induced rise in right atrial and pulmonary vascular pressures was significantly attenuated, but significant differences between the frusemide doses of 250 mg, 1.0 mg/kg, and 1.5 mg/kg were not discerned and all horses remained positive for EIPH. Although a further significant (P<0.05) attenuation of the exercise-induced rise in pulmonary capillary blood pressure occurred when frusemide dose increased from 250 mg to 2.0 mg/kg bwt, all horses still experienced EIPH. It is concluded that a linear response to increasing frusemide dosage in terms of attenuation of the pulmonary capillary hypertension does not exist in strenuously exercising Thoroughbred horses.     

Do Thoroughbred and Standardbred horses have similar increases in pulmonary vascular pressures during exertion?

To test the hypothesis that the pulmonary vascular pressures of Thoroughbred and Standardbred horses behave similarly during exertion. Measurements were made on 5 Thoroughbred and 5 Standardbred horses on a treadmill at rest and during 3-minute exercise intervals at speeds predicted to produce 75%, 90%, and 100% maximal heart rate. Left forelimb acceleration, heart rate, esophageal pressure, and pulmonary artery pressure were measured continuously. Pulmonary capillary and wedge pressures were measured during intermittent occlusion of the pulmonary artery. Breathing rate and gait frequency were the fundamental frequencies of the esophageal pressure and limb acceleration signals respectively. The ratio of speed:gait frequency gave stride length. The effects of exertion and breed were evaluated using two-way analysis of variance. Exertion produced significant increases in pulmonary artery (P = 0.001), capillary (P= 0.002), and wedge (P= 0.005) pressures. No significant effect of breed was detected on pulmonary artery pressure, but at exertion pulmonary capillary and wedge pressures were 15% (P= 0.03) and 23% (P= 0.04) greater in Thoroughbreds, respectively. Treadmill speed was ~12% greater (P= 0.04), stride length was ~25% greater (P= 0.0003), gait frequency was ~10% less (P= 0.006), breathing rate was ~10% less (P= 0.001), and heart rate was ~6% less (P= 0.06) for Thoroughbreds. There was no effect of breed on inspiratory or expiratory esophageal pressure although mean esophageal pressure was ~2 mmHg greater (P= 0.03) in exercising Standardbreds. In conclusion, pulmonary capillary and wedge pressures are greater in Thoroughbreds than in Standardbreds at similar fractions of maximal heart rate. This is compatible with the higher incidence of exercise-induced pulmonary hemorrhage observed in Thoroughbreds.     

Hemodynamic effects of ionized calcium in horses anesthetized with halothane or isoflurane

OBJECTIVES: To evaluate the effects of halothane and isoflurane on cardiovascular function and serum total and ionized calcium concentrations in horses, and to determine whether administration of calcium gluconate would attenuate these effects. ANIMALS: 6 clinically normal adult Thoroughbreds. PROCEDURE: Catheters were inserted for measurement of arterial blood pressures, pulmonary arterial blood pressures, right ventricular pressure (for determination of myocardial contractility), right atrial pressure, and cardiac output and for collection of arterial blood samples. Anesthesia was then induced with xylazine hydrochloride and ketamine hydrochloride and maintained with halothane or isoflurane. An i.v. infusion of calcium gluconate was begun 75 minutes after anesthetic induction; dosage of calcium gluconate was 0.1 mg/kg of body weight/min for the first 15 minutes, 0.2 mg/kg/min for the next 15 minutes, and 0.4 mg/kg/min for an additional 15 minutes. Data were collected before, during, and after administration of calcium gluconate. RESULTS: Halothane and isoflurane decreased myocardial contractility, cardiac index, and mean arterial pressure, but halothane caused greater depression than isoflurane. Calcium gluconate attenuated the anesthetic-induced depression in cardiac index, stroke index, and maximal rate of increase in right ventricular pressure when horses were anesthetized with isoflurane. When horses were anesthetized with halothane, a higher dosage of calcium gluconate was required to attenuate the depression in stroke index and maximal rate of increase in right ventricular pressure; cardiac index was not changed with calcium administration. CONCLUSIONS AND CLINICAL RELEVANCE: I.v. administration of calcium gluconate may support myocardial function in horses anesthetized with isoflurane.     

Pulmonary artery wedge pressure and heart rate measurement during pharmacological stress induction for left cardial function diagnosis in horses with and without heart disease

In 18 horses, the pulmonary artery wedge pressure and the heart rate were measured during pharmacological stress load. 12 horses were healthy (4 trained, 8 untrained) and 6 horses had a heart disease (3 trained, 3 untrained). Pharmacological stress induction was carried out with the sympathomimetic drug dobutamine at a dosage rate of 7.5 microg/kg/min over 10 minutes of infusion. At the fourth minute, the parasympatholytic drug atropine was administered (5 microg/kg bw), and the heart rate and the pulmonary artery wedge pressure were continuously measured over 26 minutes. During sole dobutamine infusion, a significant decrease in heart rate and a significant increase in pulmonary artery wedge pressure were observed. After the application of atropine in the fourth minute, a significant increase in heart rate (from 35.7 +/- 6 up to 106 +/- 38/ min) and in pulmonary artery wedge pressure (from 15.7 +/- 3 up to 24 +/- 8.6 mmHg) were visible in the group of healthy horses. The horses with heart diseases had a significantly higher increase in both parameters (heart rate and pulmonary artery wedge pressure) with a significantly positive correlation (r = 0.7). The heart rate increased in the horses with heart diseases from 35.2 +/- 2,8 beats/min up to 132 +/- 45.7 beats/min and the pulmonary artery wedge pressure increased from 17.3 +/- 3,2 mmHg up to 32.7 +/- 13 mmHg. The cardiac status (healthy or heart disease) as well as the training level of the horses (untrained or trained) had a significant influence on the heart rate and the pulmonary artery wedge pressure. The untrained horses (healthy and heart disease) showed significantly higher values over a longer period of time than did the trained horses with the same cardiac status. Additionally the influence of pharmacological stress induction on echocardiographic parameters was investigated. The left atrial size (p = 0.015) and left ventricular diameter were significanly different in the systole (p = 0.008) and in the diastole (p = 0.001) between healthy horses and horses with heart diseases. All horses showed a positive correlation between the pulmonary artery wedge pressure and the left atrial size (r = 0.8), as well as between the left ventricular systolic (r = 0.6) and the diastolic diameter (r = 0.6). The correlation between the pulmonary artery wedge pressure and the left atrial size was nearly the same in the healthy horses (r = 0.74) and in the horses with heart diseases (r = 0.76). Regarding the training level, all untrained horses had a significantly higher correlation between the pulmonary artery wedge pressure and the left atrial size (r = 0.87) in comparison to the trained horses (r = 0.74). Particularly in the untrained horses with heart diseases, this correlation was remarcable (r = 0.99).     

Safety and efficacy of a technique for thoracoscopically guided pulmonary wedge resection in horses

OBJECTIVE: To evaluate the safety and efficacy of thoracoscopically guided pulmonary wedge resection in horses. ANIMALS: 10 horses (5 control horses and 5 horses affected with recurrent airway obstruction [ie, heaves]). PROCEDURE: Each horse underwent a thoracoscopically guided pulmonary wedge resection. Before, during, and after surgery, heart rate, respiratory rate, arterial blood gases, and systemic and pulmonary arterial pressures were measured. Physical examination, CBC, and thoracic radiography and ultrasonography were performed 24 hours before and 2 and 48 hours after surgery. Pulmonary specimens were assessed by histologic examination. A second thoracoscopic procedure 14 days later was used to evaluate the resection site. RESULTS: The technique provided excellent specimens for histologic evaluation of the lung. Heart and respiratory rates decreased significantly after horses were administered sedatives. A significant transient decrease in Pao2 was detected immediately after pulmonary wedge resection, but we did not detect significant effects on arterial pH, Paco2, or mean arterial and pulmonary arterial pressures. All horses except 1 were clinically normal after thoracoscopic surgery; that horse developed hemothorax attributable to iatrogenic injury to the diaphragm. The second thoracoscopy revealed minimal inflammation, and there were no adhesions. CONCLUSIONS AND CLINICAL RELEVANCE: Thoracoscopically guided pulmonary wedge resection provides a minimally invasive method for use in obtaining specimens of lung tissues from healthy horses and those with lung disease. This technique may be useful for the diagnosis of diseases of the lungs and thoracic cavity.     

Effects of slow infusion of a low dosage of endotoxin on systemic haemodynamics in conscious horses

The effects of intravenous (iv) infusion of endotoxin for 60 mins at a cumulative dosage of 0.03 micrograms/kg bodyweight on systemic arterial, right atrial and pulmonary arterial pressures, heart rate, cardiac output, and derived pulmonary vascular resistance and total peripheral vascular resistance were compared to the effects of iv infusion of saline solution in four healthy horses. Heart rate was increased significantly after endotoxin infusion, although diastolic arterial pressure, systolic arterial pressure, electronically averaged arterial pressure, cardiac output, total peripheral resistance, and right atrial pressure did not change significantly. Average pulmonary arterial pressure was increased significantly by endotoxin infusion. This was accompanied by a trend toward increased diastolic pulmonary arterial pressure (P = 0.1), systolic pulmonary arterial pressure (P = 0.08) and pulmonary vascular resistance (P = 0.07). These results suggest that low dosages of endotoxin produce pulmonary hypertension without causing hypotensive, hypodynamic shock.     

Ureteral ligation prevents the haemodynamic effect of frusemide in pentobarbitol anaesthetised horses

Frusemide reduces pulmonary vascular pressures in resting horses and attenuates exercise-induced increases in these pressures in exercising horses. The mechanism underlying these effects of frusemide is unclear. We tested the hypothesis that the haemodynamic effects of frusemide are dependent on diuresis by examining the effect of frusemide in anaesthetised horses in which diuresis was prevented by ligation of ureters. Twenty four horses were assigned randomly to one of 4 treatments: 1) frusemide (1 mg/kg bwt i.v.) and intact ureters; 2) frusemide and ligated ureters; 3) saline placebo and ligated ureters; and 4) frusemide and phenylbutazone (4.4 mg/kg bwt i.v. 12 h and 15 min before frusemide) and ligated ureters. Frusemide administration to anaesthetised horses with intact ureters increased plasma total protein concentration and reduced mean right atrial, pulmonary artery and aortic pressures. There was no significant effect of frusemide administration on haemodynamic variables or plasma total protein concentration in horses with ligated ureters. The combination of frusemide and phenylbutazone increased mean right atrial, pulmonary artery and aortic pressures in horses with ligated ureters. This study demonstrates that, in anaesthetised horses, the haemodynamic effect of frusemide is dependent upon diuresis. We interpret these results as providing further evidence that the haemodynamic effect of frusemide in horses is attributable to a reduction in plasma and blood volume.     

Pharmacology of Furosemide in the Horse: A Review

Furosemide, a diuretic, is frequently administered to horses for the prophylaxis of exercise-induced pulmonary hemorrhage and the treatment of a number of clinical conditions, including acute renal failure and congestive heart failure. Furosemide increases the rate of urinary sodium, chloride, and hydrogen ion excretion. Plasma potassium concentration decreases after furosemide administration but urinary potassium excretion in horses is minimally affected. Renal blood flow increases after furosemide administration. Systemically, furosemide increases venous compliance and decreases right atrial pressure, pulmonary artery pressure, pulmonary artery wedge pressure, and pulmonary blood volume. The systemic hemodynamic effects of furosemide are only manifest in the presence of a functional kidney, but can occur in the absence of diuresis, emphasizing the importance of the renal-dependent extra-renal effects of furosemide. The renal and systemic hemodynamic effects of furosemide are modified by prior administration of nonsteroidal anti-inflammatory drugs. Furosemide administration attenuates exercise-induced increases in right atrial, aortic, and pulmonary artery pressures in ponies. Furosemide prevents exercise and allergen-induced bronchoconstriction in humans and decreases total pulmonary resistance in ponies with recurrent obstructive airway disease. These pharmacologic effects are frequently used to rationalize its questionable efficacy in the prevention of exercise-induced pulmonary hemorrhage. Neither the effect of furosemide on athletic performance nor its efficacy in the prevention of exercise-induced pulmonary hemorrhage has been convincingly demonstrated.     

Effects of an endothelin receptor antagonist and nitroglycerin on digital vascular function in horses during the prodromal stages of carbohydrate overload-induced laminitis

OBJECTIVE: To evaluate changes in digital vascular function in horses with carbohydrate overload (CHO)-induced laminitis and determine the effects of an endothelin (ET) receptor antagonist and nitroglycerin on laminitis-associated vascular dysfunction. ANIMALS: 20 adult horses without abnormalities of the digit. PROCEDURES: Hemodynamic variables were recorded before (baseline) and hourly after all horses were administered a CHO ration via nasogastric tube. In 4 groups of 5 horses each, saline (0.9% NaCl) solution or ET receptor antagonist (10(5)M in digital blood) was administered into the digital arterial circulation according to 1 of 2 schedules. During anesthesia, blood flow; arterial, venous, and capillary pressures; and total, precapillary, and postcapillary resistances were measured in an isolated perfused digit of each horse. In all groups, nitroglycerin was infused (10(5)M in digital blood), and digital microvascular assessments were repeated. RESULTS: The CHO caused a significant decrease in right atrial pressure by 14 hours that was not affected by administration of saline solution or ET receptor antagonist. In isolated digits of anesthetized horses, CHO resulted in a significant decrease in digital blood flow associated with a significant increase in total and postcapillary resistances. Treatment with the ET receptor antagonist and nitroglycerin caused a significant decrease in total resistance. Postcapillary resistance was significantly decreased following treatment with the ET receptor antagonist but was not altered by treatment with nitroglycerin. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with an ET receptor antagonist and nitroglycerin resulted in significant improvement in vascular resistance in isolated perfused digits of anesthetized horses with CHO-induced laminitis.     

Hemodynamic and metabolic alterations associated with intravenous infusion of a combination of adenosine triphosphate and magnesium chloride in conscious horses.

OBJECTIVE: To determine hemodynamic and metabolic effects of IV infusion of ATP-MgCl2 combination and maximal safe IV infusion rate in conscious horses. ANIMALS: 6 adult female horses. PROCEDURE: All horses received an IV infusion of ATP-MgCl2 combination, beginning at a rate of 0.05 mg of ATP/kg of body weight/min, which was increased by 0.05 mg/kg/min increments at 10-minute intervals until a rate of 1.0 mg/kg/min was achieved. Data were collected prior to the start of the infusion, at the end of each infusion rate, and at 15-minute intervals for the next hour after discontinuation of the infusion. Measured or calculated hemodynamic variables included cardiac output, cardiac index, heart rate, stroke volume, systemic and pulmonary arterial pressures, and systemic and pulmonary vascular resistances. Arterial blood gas tensions, CBC, plasma biochemical profiles, urine volume and specific gravity, and selected clinical signs of disease also were evaluated. RESULTS: Intravenous infusion of ATP-MgCl2 significantly increased cardiac output, decreased systemic vascular resistance, and caused mild pulmonary hypertension. Magnitude of the hemodynamic alterations was dependent on rate of infusion. Maximal safe infusion rate for these horses was 0.3 mg/kg/min. All horses became lethargic, and their appetites diminished during the infusion; 5 horses had mild signs of abdominal discomfort. Flank sweating was observed in all horses as infusion rate increased. Urine volume and specific gravity and hematologic, biochemical, and arterial blood gas alterations were detected during and after infusion. CONCLUSIONS AND CLINICAL RELEVANCE: Intravenous administration of ATP-MgCl2 in healthy, conscious, adult horses caused various metabolic and hemodynamic alterations that were without appreciable detrimental effects.     

Effects of two different dosages of dobutamine on pulmonary artery wedge pressure, systemic arterial blood pressure and heart rate in anaesthetized horses

The purpose of the present study was to investigate the effects of two different dobutamine concentrations on pulmonary artery wedge pressure (PAWP) and on mean systemic arterial blood pressure (MAP) in horses anaesthetized with isoflurane, after induction of general anaesthesia with xylazine, ketamine and diazepam. Eight healthy warm-blood horses were included in the study. Each horse was subjected to general anaesthesia twice with two different dosages of dobutamine, 3 and 5 microg/kg bw/min, being infused over 15 min, starting 50 min after induction of general anaesthesia (T(0)). The heart rate, the PAWP and the MAP were recorded after 10 min (T(1)) and then every 5 min until 15 min after cessation of intravenous dobutamine administration (T(3)-T(5)). The PAWP was measured by a right heart catheter, which was positioned in the pulmonary capillaries. Mean systemic arterial blood pressure was monitored at the facial artery for the duration of general anaesthesia. All parameters increased at both dosage rates of dobutamine and decreased significantly when dobutamine administration ceased. The increase in heart rate was significantly higher after administration of 3 microg/kg bw/min dobutamine compared with the dosage of 5 microg/kg bw/min dobutamine. The increase in MAP was also higher at this dosage, but not significantly different to the dosage of 5 microg/kg bw/min dobutamine. During both dosages the MAP was above a value considered to be compatible with good peripheral circulation. The greater increase in PAWP was observed during administration of 5 g/kg bw/min dobutamine, but PAWP was not significantly different with the dosage of 3 microg/kg bw/min dobutamine. In conclusion, the administration of dobutamine led to an increase in MAP and PAWP above a value considered to be compatible with a good peripheral circulation. The results of the present study indicate that dobutamine improves circulation, in addition to its well-known effect on the periphery.     

Effect of phenylbutazone on the haemodynamic, acid-base and eicosanoid responses of horses to sustained submaximal exertion

The systemic haemodynamic and acid-base effects of the administration of phenylbutazone (4·4 mg kg⁻¹ intravenously) to standing and running horses were investigated. Phenylbutazone, or a placebo, was administered to each of six mares either 15 minutes before, or after 30 minutes of a 60-minute submaximal exercise test which elicited heart rates approximately 55 per cent of maximal, and to the same horses at rest. The variables examined included the cardiac output, heart rate, systemic and pulmonary arterial pressures, right atrial and right ventricular pressures, and arterial and mixed venous blood gases and pH. Serum sodium, potassium and chloride concentrations, and plasma thromboxane B₂, 6-keto-prostaglandin F_1α (6-keto-PGF_1α), and prostaglandin E₂ (PGE₂) concentrations were measured in separate studies using similar protocols in the same horses. Running produced increases in heart rate, cardiac output, mean arterial and right ventricular pressure, and decreases in total peripheral resistance. The acid:base responses to exertion were characterised by respiratory alkalosis. Exertion did not significantly influence plasma 6-keto-PGF_1α or PGE₂ concentrations but plasma thromboxane B₂ concentrations were increased significantly by 60 minutes of exertion in the untreated horses. This exercise-induced increase in plasma thromboxane B₂ concentration was inhibited by the previous administration of phenylbutazone, but phenylbutazone did not produce detectable changes in systemic haemodynamic or acid-base variables in either standing or running horses.     

Effect of a 30-minute infusion of dobutamine hydrochloride on hind limb blood flow and hemodynamics in halothane-anesthetized horses

OBJECTIVE: To evaluate the hemodynamic effects of dobutamine hydrochloride (0.5 microg/kg of body weight/min) in halothane-anesthetized horses. ANIMALS: 6 adult Thoroughbred horses. PROCEDURE: Anesthesia was induced by use of romifidine (100 microg/kg) and ketamine (2.2 mg/kg), IV. Anesthesia was maintained by halothane (end-tidal concentration 0.9 to 1.0%). Aortic, left ventricular, and right atrial pressures were measured, using catheter-mounted strain gauge transducers. Cardiac output (CO), velocity time integral, maximal aortic blood flow velocity and acceleration, and left ventricular preejection period and ejection time were measured from aortic velocity waveforms obtained by transesophageal Doppler echocardiography. Velocity waveforms were recorded from the femoral vessels, using Doppler ultrasonography. The time-averaged mean velocity and early diastolic deceleration slope (EDDS) were measured. Pulsatility index (PI) and volumetric flow were calculated. Microvascular perfusion was measured in the semimembranosus muscles by laser Doppler flowmetry. Data were recorded 60 minutes after induction of anesthesia (control) and at 15 and 30 minutes after start of an infusion of dobutamine (0.5 microg/kg/min). RESULTS: Aortic pressures were significantly increased during the infusion of dobutamine. No change was observed in the indices of left ventricular systolic function including CO. Femoral arterial flow significantly increased, and the PI and EDDS decreased. No change was observed in the femoral venous flow or in microvascular perfusion. CONCLUSIONS AND CLINICAL RELEVANCE: At this dosage, dobutamine did not alter left ventricular systolic function. Femoral blood flow was preferentially increased as the result of local vasodilatation. The lack of effect of dobutamine on microvascular perfusion suggests that increased femoral flow is not necessarily associated with improved perfusion of skeletal muscles.     

Cardiopulmonary evaluation of the use of medetomidine hydrochloride in cats.

OBJECTIVE: To evaluate the cardiovascular effects of the alpha2-adrenergic receptor agonist medetomidine hydrochloride in clinically normal cats. ANIMALS: 7 clinically normal cats. PROCEDURE: Cats were anesthetized with isoflurane, and thermodilution catheters were placed for measurement of central venous, pulmonary, and pulmonary capillary wedge pressures and for determination of cardiac output. The dorsal pedal artery was catheterized for measurement of arterial blood pressures and blood gas tensions. Baseline variables were recorded, and medetomidine (20 microg/kg of body weight, IM) was administered. Hemodynamic measurements were repeated 15 and 30 minutes after medetomidine administration. RESULTS: Heart rate, cardiac index, stroke index, rate-pressure product, and right and left ventricular stroke work index significantly decreased from baseline after medetomidine administration, whereas systemic vascular resistance and central venous pressure increased. However, systolic, mean, and diastolic arterial pressures as well as arterial pH, and oxygen and carbon dioxide tensions were not significantly different from baseline values. CONCLUSIONS AND CLINICAL RELEVANCE: When administered alone to clinically normal cats, medetomidine (20 microg/kg, IM) induced a significant decrease in cardiac output, stroke volume, and heart rate. Arterial blood pressures did not increase, which may reflect a predominant central alpha2-adrenergic effect over peripheral vascular effects.     

Cardiovascular effects of romifidine in dogs

OBJECTIVE: To characterize the cardiovascular effects of romifidine at doses ranging from 5 to 100 microg/kg of body weight, IV. ANIMALS: 25 clinically normal male Beagles. PROCEDURE: Romifidine was administered IV at a dose of 5, 10, 25, 50, or 100 microg/kg (n = 5/group). Heart rate, arterial pressure, central venous pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, body temperature, cardiac output, and PCV were measured immediately prior to and at selected times after romifidine administration. Cardiac index, stroke index, rate-pressure product, systemic and pulmonary vascular resistance indices, and left and right ventricular stroke work indices were calculated. Degree of sedation was assessed by an observer who was blinded to the dose administered. RESULTS: Romifidine induced a decrease in heart rate, pulmonary arterial pressure, rate-pressure product, cardiac index, and right ventricular stroke work index and an increase in central venous pressure, pulmonary capillary wedge pressure, and systemic vascular resistance index. In dogs given romifidine at a dose of 25, 50, or 100 microg/kg, an initial increase followed by a prolonged decrease in arterial pressure was observed. Arterial pressure immediately decreased in dogs given romifidine at a dose of 5 or 10 microg/kg. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that IV administration of romifidine induces dose-dependent cardiovascular changes in dogs. However, the 2 lowest doses (5 and 10 microg/kg) induced less cardiovascular depression, and doses > or = 25 microg/kg induced similar cardiovascular changes, suggesting that there may be a ceiling on the cardiovascular effects of romifidine.