Haemodynamic effects of ATP in dogs during hypoxia-induced pulmonary hypertension

Pulmonary hypertension may result from an increase in vascular resistance caused by persistent hypoxia. We have investigated the effects of adenosine triphosphate (ATP), administered into the pulmonary artery, on haemodynamic changes occurring in anaesthetized adult dogs subjected to acute hypoxic pulmonary vasoconstriction. Hypoxia alone (ventilation with 10% O2/90% N2) caused significant increases in mean pulmonary arterial blood pressure (PAP), central venous pressure (CVP), and cardiac index (CI) by 71, 102 and 38%, respectively. ATP (0.03-3.0 micromol/kg/min approximately 0.02-1.65 mg/kg/min), when infused under hypoxic conditions, significantly reduced both mean PAP and systemic arterial blood pressure (ABP) in a dose-dependent manner. The maximum decrease in mean PAP amounted to 20%; mean ABP, on the other hand, was decreased by up to 52% (P<0.01). Heart rate, CI, CVP and pulmonary occlusion pressure were not dose-dependently affected by ATP. Our data indicate that while pulmonary arterial administration of ATP in mature dogs during hypoxic pulmonary hypertension causes dilation in the pulmonary vascular bed, it is even more effective in dilating the systemic vasculature. This result suggests a need for further evaluation and warrants cautious use of ATP in the treatment of hypoxic pulmonary hypertension in adult dogs.     

Sodium hydrosulfide prevents hypoxia-induced pulmonary arterial hypertension in broilers

1. The aim of the study was to determine if H₂S is involved in the development of hypoxia-induced pulmonary hypertension in broilers, a condition frequently observed in a variety of cardiac and pulmonary diseases.

2. Two-week-old broilers were reared under normoxic conditions or exposed to normobaric hypoxia (6?h/day) with tissue levels of H₂S adjusted by administering sodium hydrosulfide (NaHS, 10?µmol/kg body weight/day). Mean pulmonary arterial pressure, right ventricular mass, plasma and tissue H₂S levels, the expression of cystathionine-β-synthase (CSE) and vascular remodeling were determined at 35?d of age.

3. Exposure to hypoxia-induced pulmonary arterial hypertension was characterized by elevated pulmonary pressure, right ventricular hypertrophy and vascular remodeling. This was accompanied by decreased expression of CSE and decreased concentrations of plasma and tissue H₂S.

4. Hypoxia-induced pulmonary hypertension was significantly reduced by administration of NaHS but this protective effect was largely abolished by D, L-propargylglycerine, an inhibitor of CSE.

5. The results indicate that H₂S is involved in the development of hypoxia-induced pulmonary hypertension. Supplementing NaHS or H₂S could be a strategy for reducing hypoxia-induced hypertension in broilers.     

Hemodynamic response of endotoxemic calves to treatment with small-volume hypertonic saline solution

The hemodynamic effects of hypertonic saline solution (HSS) resuscitation on endotoxic shock were examined in pentobarbital-anesthetized calves (8 to 20 days old). Escherichia coli (055:B5) endotoxin was infused IV at dosage of 0.1 microgram/kg of body weight for 30 minutes. Endotoxin induced large decreases in cardiac index, stroke volume, maximal rate of change of left ventricular pressure (+dP/dtmax), femoral and mesenteric arterial blood flow, glomerular filtration rate, urine production, and mean aortic pressure. Severe pulmonary arterial hypertension and increased pulmonary vascular resistance were evident at the end of endotoxin infusion. Treatment with HSS (2,400 mosm of NaCl/L, 4 ml/kg) or an equivalent sodium load of isotonic saline solution (ISS: 300 mosm of NaCl/L, 32 ml/kg) was administered 90 minutes after the end of endotoxin administration. Both solutions were infused IV over a 4- to 6-minute period. Administration of HSS induced immediate and significant (P less than 0.05) increase in stroke volume and central venous pressure, as well as significant decrease in pulmonary vascular resistance. These effects were sustained for 60 minutes, after which all variables returned toward preinfusion values. The hemodynamic response to HSS administration was suggestive of rapid plasma volume expansion and redistribution of cardiac output toward splanchnic circulation. Plasma volume expansion by HSS was minimal 60 minutes after resuscitation. Administration of ISS induced significant increase in cardiac index, stroke volume, femoral arterial blood flow, and urine production. These effects were sustained for 120 minutes, at which time, calves were euthanatized. Compared with HSS, ISS induced sustained increase in mean pulmonary arterial pressure and only a small increase in mesenteric arterial blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical Characteristics of 53 Dogs with Doppler-Derived Evidence of Pulmonary Hypertension: 1992–1996

Pulmonary hypertension occurs as a primary or secondary disorder of the pulmonary vasculature. Doppler echocardiography provides a noninvasive tool for the estimation of pulmonary arterial pressure when tricuspid regurgitation or pulmonic insufficiency is present. The cardiology database at Colorado State University was reviewed, and echocardiographic records from cases diagnosed with pulmonary hypertension were evaluated. Application of the modified Bernoulli equation to the maximal instantaneous velocity of a right-sided regurgitant jet provided evidence of pulmonary hypertension in 53 dogs over a 4-year period. Tricuspid regurgitant velocity > or = 2.8 m/second or pulmonic insufficiency velocity > or = 2.2 m/second was considered abnormal and indicative of pulmonary hypertension. Tricuspid regurgitant gradients in 51 dogs ranged from 32 to 145 mm Hg (mean, 63.0 mm Hg; median, 57.0 mm Hg; 25th-75th percentiles, 45.2-76.5 mm Hg). Pulmonic insufficiency gradients in 8 dogs ranged from 20 to 100 mm Hg (mean, 59.5 mm Hg; median, 61.5 mm Hg; 25th-75th percentiles, 32.0-84.5 mm Hg). Affected dogs ranged in age from 2 months to 16 years. Clinical signs were characteristic of cardiopulmonary disease, but a relatively high frequency of syncope was noted (12 of 53 dogs, 23%). Pulmonary hypertension was probably due to increased pulmonary vascular resistance in 23 dogs, pulmonary overcirculation in 2 dogs, and pulmonary venous hypertension in 23 dogs. Five dogs lacked a clinically recognizable cardiopulmonary cause of pulmonary vascular disease. Our results suggest that pulmonary hypertension can occur as a complication of commonly encountered cardiopulmonary diseases, and that Doppler echocardiography can facilitate recognition of this condition.     

Hypoxic pulmonary hypertension in the pony.

Hemodynamic measurements were made in 6 ponies at low altitude (Madison, WI, altitude, 250 m) and after 1, 2, 4, and 6 weeks at high altitude (Climax, CO, altitude, 3,400 m). The salient findings were that ponies maintain an increased heart rate and cardiac output and develop significant pulmonary hypertension at high altitude. The average control resting mean pulmonary artery pressure (BPpul) was 25.1 mm of Hg at 250 m; this value increased to 56.3 mm of Hg after 6 weeks at 3,400 m. An additional finding was that the pulmonary vascular response to acute hypoxia seemed to increase with time at high altitude.     

Effects of ketanserin on pulmonary hemodynamics, lung mechanics, and gas exchange in endotoxemic pigs

The effects of ketanserin on pulmonary hemodynamics, lung mechanics, and gas exchange were determined in anesthetized 10- to 14-week-old pigs after they were endotoxemic for 1 or 4.5 hours. Saline solution was given to controls (group 1). Escherichia coli endotoxin (055-B5) was infused IV at a dosage of 5 micrograms/kg for 1 hour (group 2). In group 3, endotoxin was infused at 5 micrograms/kg the first hour plus a continuous infusion of endotoxin at 2 micrograms/kg/hr. Ketanserin, a specific serotonin receptor antagonist, was infused IV (300 micrograms/kg) after pigs were endotoxemic for 1 or 4.5 hours (groups 2 and 3, respectively). At 1 hour of endotoxemia, mean pulmonary artery pressure and pulmonary vascular resistance were increased, and cardiac index was decreased. Ketanserin caused a small attenuation of the increases in mean pulmonary artery pressure and pulmonary vascular resistance, indicating that serotonin may have a small role in the endotoxin response at 1 hour. At 4.5 hours of endotoxemia, mean pulmonary artery pressure, pulmonary vascular resistance, alveolar dead space ventilation, and alveolar-arterial oxygen gradient were increased, and cardiac index and lung dynamic compliance were decreased; ketanserin significantly attenuated the endotoxin-induced changes in cardiac index, mean pulmonary artery pressure, pulmonary vascular resistance, and lung dynamic compliance. Ketanserin also decreased the blood temperature after pigs were endotoxemic for 4.5 hours. However, the endotoxin-induced increases (at 4.5 hours) in alveolar-arterial oxygen gradient and alveolar dead space ventilation were not acutely reversed by ketanserin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plexogenic pulmonary arteriopathy in a Pembroke Welsh corgi

A 21-month-old, male Pembroke Welsh corgi was referred for investigation of respiratory distress and progressive lethargy. Cardiac evaluation revealed a grade 4 pansystolic murmur over the left and right heart base. A heart murmur, dyspnoea, cyanosis, prolonged capillary refill time and ascites led to the tentative diagnosis of a cardiac malformation with a right-to-left shunt, with likely additional pulmonary disease. Pulmonary hypertension became evident during echocardiography, when the estimated systolic pulmonary artery pressure was over 70 mmHg. Angiography revealed abnormal pulmonary vascular markings consistent with pulmonary hypertension and a small right-to-left shunting patent ductus arteriosus (PDA). The diagnosis of PDA was confirmed at postmortem examination. Histology of the pulmonary arteries showed lesions of plexogenic pulmonary arteriopathy. The question of whether both conditions were separate or part of the same clinical syndrome is discussed in this report.     

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.     

Pulmonary dysfunction in neonatal calves after intratracheal inoculation of small volumes of fluid

Intratracheal instillation of 20 ml of room temperature (21 to 24 C) fluid in anesthetized neonatal calves resulted in rapid onset of reversible pulmonary dysfunction. Arterial O2 tension and dynamic compliance decreased, whereas pulmonary arterial pressure, pulmonary vascular resistance, alveolar arterial O2 difference, and total pulmonary resistance increased from base-line values. Abnormalities of gas exchange and pulmonary mechanics were induced by intratracheal fluid instillation whether or not Pasteurella haemolytica was in the inoculum. Physical manipulation of the calf without intratracheal fluid instillation (sham inoculation) did not influence pulmonary function. Bilateral vagotomy eliminated the increase in pulmonary resistance and the decrease in dynamic compliance, but did not eliminate hypoxemia, increased alveolar arterial O2 difference, or pulmonary hypertension recorded after intratracheal fluid instillation. Seemingly, changes in pulmonary mechanics are mediated via the vagus nerve. However, one or more additional mechanisms must be responsible for the hypoxemia and pulmonary hypertension.     

Cardiac effects of pulmonary disease.

Pulmonary hypertension (PHT) is the primary cardiac consequence of pulmonary disease. It develops as alveolar hypoxia of pulmonary disease, coupled with vasoactive and mitogenic substances released from pulmonary endothelial and vascular smooth muscle cells damaged by the primary disease process, mediates arterial vasoconstriction and vascular remodeling to raise pulmonary vascular resistance. Independent of the underlying pulmonary disease, PHT produces clinical signs of respiratory distress, exercise intolerance, syncope, and right heart failure. Diagnosis of PHT is made by estimation of pulmonary artery pressures by means of continuous-wave Doppler echocardiographic assessment of tricuspid or pulmonic regurgitant flow velocity. Treatment of PHT is directed at the underlying pulmonary disease but may also aim to attenuate pulmonary artery pressure and limit the clinical sequelae of PHT. No treatments are of proven benefit in veterinary patients; irrespective of the nature of the inciting pulmonary disease, the prognosis is often grave.     

Pulmonary manifestations of heartworm disease

The clinical signs associated with heartworm disease are the result of changes in the pulmonary arterial system. These clinical signs are the result of either pulmonary hypertension or lung parenchymal disease associated with vascular changes. An increase in pulmonary arterial pressure produces an increase in right ventricular afterload, which may lead to exercise intolerance, syncope, and right-sided congestive heart failure. Coughing, dyspnea, and hemoptysis are the results of pulmonary parenchymal disease.     

Effects of extrathoracic airway obstruction on intrathoracic pressure and pulmonary artery pressure in exercising horses

OBJECTIVE: To determine whether dorsal displacement of the soft palate (DDSP) results in pulmonary artery hypertension and leads to increases in transmural pulmonary artery pressure (TPAP); to determine whether pulmonary hypertension can be prevented by prior administration of furosemide; and to determine whether tracheostomy reduces pulmonary hypertension. ANIMALS: 7 healthy horses. PROCEDURE: Horses were subjected to 3 conditions (control conditions, conditions after induction of DDSP, and conditions after tracheostomy). Horses were evaluated during exercise after being given saline (0.9% NaCl) solution or furosemide. RESULTS: Controlling for drug, horse, and speed of treadmill, DDSP-induced increase in intrathoracic pressure was associated with a significant increase in minimum (36 mm Hg), mean (82 mm Hg), and maximum (141 mm Hg) pulmonary artery pressure, compared with values for control horses (30, 75, and 132 mm Hg, respectively). Increases in pulmonary artery pressure did not induce concomitant increases in TPAP. Tracheostomy led to a significant reduction of minimum (53 mm Hg), and mean (79 mm Hg) TPAP pressure, compared with values for control horses (56 and 83 mm Hg, respectively). When adjusted for horse, speed of treadmill, and type of obstruction, all aspects of the pulmonary artery and TPAP curves were significantly decreased after administration of furosemide, compared with those for horses given saline (0.9% NaCl) solution. CONCLUSIONS: DDSP was associated with increases in pulmonary artery pressure but not with increases in TPAP. CLINICAL RELEVANCE: Expiratory obstructions such as DDSP are likely to result in pulmonary hypertension during strenuous exercise, but may not have a role in the pathogenesis of exercise-induced pulmonary hemorrhage.     

Effect of inhaled nitric oxide on the hypoxic pulmonary vasoconstrictor response in anaesthetised calves

The effect of inhaling nitric oxide in the hypoxic pulmonary vascular response was measured in five calves anaesthetised with a combination of guaiacol, ketamine and xylazine. Alveolar hypoxia was induced by means of the inhalation of a gas mixture with an inspiratory oxygen fraction of 14–18 per cent. This alveolar hypoxia resulted in a pronounced pulmonary hypertension (mean pulmonary artery pressure in hypoxic animals : 30·2 mmHg). Inhalation of 20 and 40 ppm of nitric oxide significantly attenuated the hypoxia induced pulmonary hypertension. The effect ceased once nitric oxide administration was stopped. A concentration of 40 ppm of nitric oxide fully abolished the hypoxia induced pulmonary hypertension (mean pulmonary artery pressure during inhalation of 40 ppm nitric oxide : 22·8 mmHg). Inhalation of nitric oxide had no effect on systemic arterial blood pressure nor on systemic vascular resistance. It was concluded that inhalation of 20 or 40 ppm of nitric oxide prevented a selective pulmonary vasoconstriction during alveolar hypoxia in calves, which may be helpful in the treatment of acute respiratory disorders in calves.     

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.     

The effect of dietary l-carnitine supplementation on pulmonary hypertension syndrome mortality in broilers exposed to low temperatures

Oxidative stress is involved in the development of pulmonary hypertension syndrome (PHS) in broilers. l-Carnitine has an antiperoxidative effect and supplemental l-carnitine has been revealed to increase broiler heart weight. The present study was conducted to evaluate the effect of an addition of 100 mg/kg l-carnitine to the basal diets on PHS mortality in cold-exposed broilers. Two-hundred and forty mixed-sex broilers were equally assigned to three groups. The control group was reared in normal temperatures throughout the experiment. Starting on day 14 continuing until the end of the experiment, the other two groups were subjected to a step-down temperature programme (by lowering the temperature 1-2 degrees C per day down to 12-14 degrees C) with or without l-carnitine added to the basal diets. Cold exposure increased the right/total ventricle ratio (RV/TV) and plasma malondialdehyde (MDA), reduced superoxide dismutase (SOD) and led to pulmonary vascular remodelling in birds without feeding additional l-carnitine. Supplemental l-carnitine reduced plasma MDA, increased SOD, inhibited remodelling and postponed the occurrence of PHS for 1 week in cold-exposed broilers; nevertheless, it did not significantly influence the cumulative PHS mortality (p > 0.05). On days 24 and 32, birds fed supplemental l-carnitine had lower RV/TV and higher total ventricle/body weight (p < 0.05) but unchanged right ventricle/body weight ratios (p > 0.05) compared to their cold-exposed counterparts, indicating an increase in left ventricle weight. However, from day 39 on, their RV/TV ratios were suddenly increased (p < 0.05). It was suggested that the l-carnitine-induced increase in left heart weight might partially account for the postponed occurrence of pulmonary hypertension in the early stage by elevating cardiac output, which might, in turn, lead to the resulting increase in pulmonary pressure. In view of its complex effects on cardiopulmonary haemodynamics, l-carnitine supplementation may be impractical for reducing PHS.     

Cardiopulmonary effects of dexmedetomidine in sevoflurane-anesthetized sheep with and without nitric oxide inhalation

OBJECTIVE: To determine whether inhaled nitric oxide (NO) prevents pulmonary hypertension and improves oxygenation after i.v. administration of a bolus of dexmedetomidine in anesthetized sheep. ANIMALS: 6 healthy adult sheep. PROCEDURE: In a crossover study, sevoflurane-anesthetized sheep received dexmedetomidine (2 microg/kg, i.v.) without NO (DEX treatment) or with inhaled NO (DEX-NO treatment). Cardiopulmonary variables, including respiratory mechanics, were measured before and for 120 minutes after bolus injection of dexmedetomidine. RESULTS: Dexmedetomidine induced a transient decrease in heart rate and cardiac output. A short-lived increase in mean arterial pressure (MAP) and systemic vascular resistance (SVR) was followed by a significant decrease in MAP and SVR for 90 minutes. Mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance increased transiently after dexmedetomidine injection. The Pao2 was significantly decreased 3 minutes after injection and reached a minimum of (mean +/- SEM) 13.3 +/- 78 kPa 10 minutes after injection. The decrease in Pao2 was accompanied by a sudden and prolonged decrease in dynamic compliance and a significant increase in airway resistance, shunt fraction, and alveolar dead space. Peak changes in MPAP did not differ between the 2 treatments. For the DEX-NO treatment, Pao2 was significantly lower and the shunt fraction significantly higher than for the DEX treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Inhalation of NO did not prevent increases in pulmonary arterial pressures induced by i.v. administration of dexmedetomidine. Preemptive inhalation of NO intensified oxygenation impairment, probably through increases in intrapulmonary shunting.     

Effect of splenectomy on exercise-induced pulmonary and systemic hypertension in ponies

Large increases in systemic and pulmonary arterial pressures of exercising healthy ponies have been observed. Because exercise causes a considerable increase in PCV of ponies, we examined the effect of splenectomy on exercise-induced changes in systemic and pulmonary pressures. These pressures (taken with catheter-tip micromanometers) and indicator dilution cardiac output were determined on 9 healthy ponies that had undergone splenectomy 4 to 9 weeks before the study. Data obtained at rest and during submaximal (10.5 to 11.0 mph) and maximal (14 to 15 mph) exercise from these ponies were compared with similar data from clinically normal ponies. Following splenectomy, PCV increased by only 4 vol% during maximal exercise, but cardiac output of splenectomized ponies reached values similar to those of clinically normal ponies. Despite this similarity in cardiac output, the systemic and pulmonary arterial pressures of exercising splenectomized ponies increased to significantly lower levels than those in clinically normal ponies (P less than 0.01); total pulmonary vascular resistance and total peripheral resistance decreased to values significantly less than those in clinically normal ponies (P less than 0.01). Thus, it appears that increases in blood viscosity induced by increases in PCV may contribute substantially to the pulmonary and systemic hypertension of exercise in clinically normal ponies.     

Hemodynamic response of calves to tiletamine-zolazepam-xylazine anesthesia.

Six healthy Holstein calves were anesthesized with isoflurane in O2 and instrumented for hemodynamic studies. A saphenous artery was catheterized for measurement of blood pressure and withdrawal of blood for determination of the partial pressure of carbon dioxide (PaCO2), oxygen (PaO2), and arterial pH (pHa). Respiration was controlled throughout the study. The ECG and EEG were monitored continuously. A thermodilution catheter was passed via the right jugular vein into the pulmonary artery for determination of cardiac output and measurement of central venous pressure, pulmonary arterial pressure, and pulmonary capillary wedge pressure. Baseline values (time 0) were recorded following recovery from isoflurane. Tiletamine-zolazepam (4 mg/kg)-xylazine (0.1 mg/kg) were administered IV immediately after recording baseline values. Values were again recorded at 5, 10, 20, 30, 40, 50, and 60 minutes after injection. Changes in left ventricular stroke work index, PaCO2, and pHa were insignificant. Arterial blood pressure and systemic vascular resistance increased above baseline at 5 minutes and then gradually decreased below baseline at 40 minutes, demonstrating a biphasic response. Values for pulmonary capillary wedge pressure, pulmonary arterial pressure, central venous pressure, and PaO2 were increased above baseline from 5 to 60 minutes. Stroke volume, stroke index, and right ventricular stroke work index were increased from 20 or 30 minutes to 60 minutes. Pulmonary vascular resistance increased at 10 minutes, returned to baseline at 20 minutes, and was increased again at 60 minutes. Heart rate, cardiac output, cardiac index, and rate pressure product were decreased at 5 minutes, and with the exception of cardiac output, remained so for 60 minutes. Cardiac output returned to the baseline value at 30 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anesthesia for severe mitral and tricuspid regurgitation.

Anesthesia for mitral or tricuspid regurgitation should be designed to maintain cardiac output by decreasing systemic and pulmonary vascular resistance to aortic and pulmonary outflow, respectively, and by carefully preserving venous return. A moderate increase in heart rate may be helpful with mitral regurgitation; bradycardia should be avoided. Isoflurane, halothane, or opioid anesthesia is preferred.