Prabodh M. Mehta

Effect of chronic native flow competition on internal thoracic artery grafts

Residual competitive flow from the native coronary artery has been proposed as a mechanism that reduces flow in an internal thoracic artery graft (ITA), resulting in narrowing and ultimately failure of the graft. Results from acute experiments have indicated that competitive flow from a fully patent native artery did not abolish ITA graft flow. The present study was designed to examine the consequences of dynamic flow competition between the native vessel and the ITA graft in a chronic model. Fifteen mongrel dogs underwent coronary artery bypass grafting using the pedicled left ITA anastomosed to the normal, fully patent circumflex (CFX) coronary artery. The procedure was performed through a sterile thoracotomy, without systemic cardiopulmonary bypass, using a brief local occlusion to construct the anastomosis. Intraoperatively, ITA flow was measured in situ on the chest wall, before the pedicle was mobilized. Internal thoracic artery graft and distal CFX flow were measured after the anastomosis was completed, with and without brief occlusion of the proximal CFX. Angiography was performed 72 hours, 4 weeks, and 8 weeks later; graft patency and diameter were evaluated. After 8 weeks, open-chest direct flow measurements comparable with the intraoperative assessment were obtained. Two grafts (13%) occluded early, the technical result of poor anastomotic construction. In the 13 remaining animals, all grafts were widely patent at all time points. Internal thoracic artery flow in situ averaged 10.9 +/- 7.8 mL/min (mean +/- standard deviation), and was maintained after grafting (11.5 +/- 4.4 mL/min; p = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Norepinephrine-induced left ventricular dysfunction in anesthetized and conscious, sedated dogs

These studies were conducted to evaluate effects of high dose norepinephrine infusion on left ventricular function in anesthetized and conscious dogs. Separate groups of pentobarbital anesthetized closed-chest dogs received norepinephrine infusion for 90 min followed by 1 h of recovery. Arterial pressure, electrocardiogram, two-dimensional echocardiogram and an equilibrium radionuclide angiogram were monitored. One hour following infusion of norepinephrine, left ventricular ejection fraction was reduced in a dose-dependent fashion. Fractional shortening was similarly reduced, with increased left ventricular systolic and diastolic dimensions also observed. Left ventricular end-systolic wall stress was increased at 60 min following infusion of norepinephrine but not saline: saline, 68 +/- 8, norepinephrine, 4 micrograms/kg/min, 113 +/- 8 g/cm2. The left ventricular end-systolic wall stress/fractional shortening relationship showed reduction of contractility. In 10 conscious dogs pretreated with morphine, norepinephrine at 5 micrograms/kg/min x 90 min produced similar changes to those seen in anesthetized animals. Ejection fraction was reduced from 0.69 +/- 0.3 to 0.36 +/- 0.04 at 60 min post infusion. Fractional shortening was also reduced. Left ventricular end-diastolic dimension was increased. However, when animals were followed for 1 week, complete recovery occurred within 48 h. Histology showed mild contraction band necrosis in acute experiments and mild perivascular fibrosis in chronic experiments. Therefore, norepinephrine cardiotoxicity produced significant left ventricular dilation and reduction of ejection phase indices of left ventricular function associated with reduced contractility. In chronic dogs, histologic changes were mild, and left ventricular dysfunction was reversible.

Competitive flow from a fully patent coronary artery does not limit acute mammary graft flow

The shriveled, stenotic mammary graft sometimes observed after internal mammary artery (IMA) to coronary artery bypass grafting has been attributed to competitive flow from the insufficiently stenosed native coronary vessel. To study further the effects of native coronary artery competing flow on IMA graft flow, 10 dogs (mean weight, 23.5 +/- 3.69 kg) underwent coronary artery bypass grafting using the pedicled left IMA anastomosed to a normal, fully patent proximal circumflex (CFX) coronary artery. The procedure was performed through a left thoracotomy, off pump, using a brief local occlusion to perform the anastomosis. Native in situ IMA flow, CFX flow distal to the anastomosis, and IMA graft flow were measured using calibrated electromagnetic flow probes. When the CFX proximal to the anastomosis was occluded transiently, IMA flow increased to supply 100% of the previously measured distal CFX flow (60.2 +/- 7.9 mL/min). When both the IMA graft and CFX proximal to the anastomosis were patent, total distal perfusion was maintained (58.9 +/- 7.8 mL/min) and relative IMA graft flow (26.5 +/- 3.3 mL/min) was proportional to the relative diameter of the IMA graft to the native coronary artery (r = 0.96). The mean flow in the IMA in situ on the chest wall before its division was 23.8 +/- 8.1 mL/min. These results suggest that, at least acutely in a canine model, IMA graft flow is maintained above in situ levels even when grafted to a completely patent coronary artery and that acute competitive flow probably does not cause mammary artery shriveling.

Effect of Cocaine on Left Ventricular Function Relation to Increased Wall Stress and Persistence After Treatment

BACKGROUND To determine whether alterations in left ventricular (LV) function after a cocaine infusion are due to reduced myocardial contractility or changes in loading conditions, we examined LV function in 30 morphine-sedated, closed-chest dogs. We also wanted to determine the time course of the effects of cocaine on LV function after the infusion was stopped. METHODS AND RESULTS Two-dimensional echocardiography and hemodynamics provided LV fractional shortening and end-systolic wall stress data. Radionuclide ventriculography was also performed. Four groups of dogs received saline or cocaine infusions of 10, 30, or 100 micrograms.kg-1.min-1. Cocaine was infused for 90 minutes with ECG and arterial pressure monitoring. Animals were monitored for an additional 120 minutes after the infusion ended. Arterial pressure rose over the course of the experiment in all four groups, but saline and cocaine 10 micrograms.kg-1.min-1 did not significantly change ejection fraction. Cocaine 30 and 100 micrograms.kg-1.min-1 acutely increased arterial pressure and heart rate but decreased ejection fraction from 0.64 +/- 0.06 to 0.45 +/- 0.08 and from 0.65 +/- 0.10 to 0.46 +/- 0.11, respectively. Additionally, cocaine 100 micrograms.kg-1.min-1 decreased fractional shortening from 36 +/- 9% to 23 +/- 12%. However, cocaine 30 and 100 micrograms.kg-1.min-1 also increased wall stress from 42 +/- 15 to 65 +/- 11 g/cm2 and from 37 +/- 15 to 90 +/- 33 g/cm2, respectively. These results were analyzed by use of the relation between wall stress and fractional shortening as an index of contractility. Fractional shortening after cocaine infusion was displaced downward as a result of increased wall stress rather than changes in contractility. In addition, alteration of afterload with phenylephrine (6 micrograms/kg) and sodium nitroprusside (10 micrograms/kg) before and during infusion of cocaine 100 micrograms.kg-1.min-1 showed similar regression lines for wall stress to fractional shortening. CONCLUSIONS Ejection-phase indexes of LV function were reduced by cocaine in this model of conscious, sedated dogs, but effects were attributable to increased wall stress rather than to reduced myocardial contractility. These effects persisted for at least 2 hours after the infusion was stopped.

Effect of diltiazem on norepinephrine-induced acute left ventricular dysfunction

The present study has examined the role of diltiazem as a protective agent in a canine model of norepinephrine cardiotoxicity. Effects of diltiazem, 20 micrograms/kg/min x 5 min pretreatment followed by 10 micrograms/kg/min x 90 min, or saline infusion were examined at baseline and 1 h after infusion of norepinephrine, 4 micrograms/kg/min for 90 min, in closed-chest anesthetized dogs. Left ventricular function was assessed by equilibrium radionuclide angiogram and two-dimensional echocardiogram. In 7 saline experiments, hypotension and increased heart rate were observed at 1 h post infusion. In the diltiazem-treated group (n = 7), mean arterial pressure and heart rate were unchanged. In the saline group, left ventricular ejection fraction fell from 0.50 +/- 0.04 to 0.28 +/- 0.04. Left ventricular ejection fraction was unchanged in the diltiazem-treated group: 0.52 +/- 0.03 to 0.55 +/- 0.07. Left ventricular end-diastolic volume was increased at 1 h post infusion in saline controls but not in the diltiazem-treated group. Measurement of fractional shortening from two-dimensional echocardiograms also indicated left ventricular dysfunction in the saline but not diltiazem-treated groups. Left ventricular end-systolic wall stress following norepinephrine infusion was significantly increased in the saline but not diltiazem-treated groups: 122.7 +/- 18.7 vs 67.6 +/- 19.7 g/cm2, respectively. In dogs receiving saline without norepinephrine infusion, no significant changes occurred over the course of the experiment. Histologic examination showed mild contraction band necrosis in saline controls but not in sham saline dogs. Diltiazem showed intermediate histologic evidence of injury, which was not further quantified. This study suggests that effects of norepinephrine on left ventricular function in the canine model of norepinephrine cardiotoxicity may be largely due to increased wall stress following a prolonged increase in afterload. Diltiazem pretreatment afforded significant protection of left ventricular function.

Effect of Hyperkalemia on Myocardial Depression by Verapamil in Isolated Hearts

Verapamil can produce depression of left ventricular function, delayed atrioventricular conduction, and hypotension, which can be potentiated by hyperkalemia. We sought to investigate a direct cardiac interaction between verapamil and hyperkalemia. Studies utilized isolated guinea pig hearts (Langendorff) paced at 250 beats/min. Hearts were randomly assigned to perfusion (Krebs-Henseleit buffer) with potassium concentrations ([K]+) of 1.5, 3, 6 and 9 mmol/l. Infusion of verapamil at rates of 0.2 to 60 micrograms/min (approximately 3 x 10(-8) to 10(-5) mol/l) produced concentration-dependent reduction of isovolumic left ventricular developed pressure. As [K]+ increased, concentration response curves showed parallel shifts to the left. The ED50 for reduction of left ventricular developed pressure significantly decreased: 8.2 +/- 3.7, 2.9 +/- 1.4, 1.2 +/- 0.7, 0.6 +/- 0.2 micrograms/min (mean +/- SD), respectively. Nifedipine and diltiazem were also studied in hearts perfused with 3 and 9 nmol/l [K]+. Infusion of nifedipine 0.003-1 microgram/min (approximately 10(-9) to 3 x 10(-7) mol/l) produced concentration-dependent reduction of left ventricular developed pressure but the ED50 was not affected by [K]+: 0.06 +/- 0.03 and 0.05 +/- 0.04 microgram/min, respectively. Nifedipine vehicle was without effect at the infusion rates tested. Infusion of diltiazem 2-200 micrograms/min (approximately 3 x 10(-7) to 3 x 10(-5) mol/l) also produced concentration-dependent reduction of left ventricular developed pressure. The ED50 for diltiazem-induced reduction of left ventricular developed pressure was significantly reduced by elevated [K]+: 20.1 +/- 6.7 and 3.5 +/- 0.9 micrograms/min with 3 and 9 mmol/l [K]+, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Discrepancies Between Doppler‐ and Catheter‐Derived Gradients in Aortic Prosthetic Valves:

Doppler‐ and catheter‐derived gradients have correlated well in patients with native aortic valvular stenosis. This relationship, however, is less certain in the presence of prosthetic aortic valves. We report a case with prosthetic aortic valve in which the echocardiogram suggested significant mechanical valve stenosis. The patient had no evidence of prosthetic valve dysfunction during cardiac catheterization. We conclude that Doppler‐derived gradients across prosthetic aortic valves should be correlated with the patients clinical condition and supplemented by additional noninvasive and invasive data obtained during cardiac catheterization when warranted.