Jon Lekven

Importance of Free Fatty Acids as a Determinant of Myocardial Oxygen Consumption and Myocardial Ischemic Injury during Norepinephrine Infusion in Dogs

Increased delivery of free fatty acids raises myocardial oxygen consumption (MVO(2)) without influencing mechanical performance. The effects of norepinephrine on MVO(2) and on the size of ischemic injury after acute coronary occlusion were therefore studied before and during inhibition of lipolysis with beta-pyridylcarbinol. In spite of similar mechanical responses to norepinephrine, MVO(2) increased by 57+/-11% before and significantly less, 31+/-6%, (P < 0.01) during inhibition of lipolysis. After coronary occlusion the ischemic injury associated with norepinephrine infusion, as evidenced by epicardial mapping of S-T segment elevation, was larger before (7.9+/-1.1 mV) than during inhibited lipolysis (2.8+/-0.4 mV; P < 0.005). Average S-T segment elevation associated with norepinephrine infusion during inhibited lipolysis (2.8+/-0.4 mV) was even lower (P < 0.05) than during control occlusion alone, before drug administration (4.4+/-0.7 mV). In conjunction with an antilipolytic agent, norepinephrine was shown to reduce the extent and magnitude of the myocardial ischemic injury produced by acute coronary occlusion; this could be due to an improved balance between myocardial oxygen supply and requirement.

Compensatory mechanisms during graded myocardial ischemia

Abstract Hemodynamic and metabolic compensatory mechanisms in myocardial ischemia were studied in anesthetized dogs. Ischemia was produced by graded reduction in coronary blood flow in hearts in which the left coronary artery was perfused through a shunt from a carotid artery. Despite a reduction in myocardial oxygen supply of as much as 20 percent, cardiac output remained unchanged. At reductions in myocardial oxygen supply of 20 to 50 percent of control value, cardiac output was maintained, but at a lower level. Further reduction was not compatible with stable hemodynamic conditions. Reduction in coronary blood flow was closely associated with concomitant ventricular dilatation and reduced myocardial contractility, and this finding could explain the maintained cardiac output at a reduced level of myocardial oxygen supply. Decreased myocardial contractility reduced myocardial oxygen demand, whereas ventricular dilatation maintained stroke volume on a geometric basis. These alterations in myocardial mechanics were found to be the most important compensatory mechanism in reduced myocardial oxygen supply; the contributions of increased myocardial oxygen extraction and myocardial anaerobiosis were of minor significance.

Myocardial function of the interventricular septum. Effects of right and left ventricular pressure loading before and after pericardiotomy in dogs.

We examined the function of the interventricular septum in six open-chest dogs by inserting piezoelectric crystals into the interventricular septum. Continuous ultrasonic recordings showed that the changes in myocardial chord length (MCL) in the septum and free walls of the right and left ventricle were similar during saline infusion and during pericardiotomy. End-diastolic MCL and myocardial shortening during ejection (MS) rose in the septum and free walls of both ventricles during saline infusion as end-diastolic pressures rose by an average of 6 mm Hg to 12–13 nun Hg. Subsequent pericardiotomy increased end-diastolic MCL and MS in the septum and free walls of the ventricles, and reduced end-diastolic pressures by 1–2 mm Hg. The responses to aortic and pulmonary artery constrictions were similar before and after pericardiotomy. When aortic constriction had raised left ventricular systolic pressure by about 60 mm Hg, end-diastolic MCL increased in the septum and free left ventricular wall, whereas end-diaetolic MCL and MS of the free right ventricular wall fell. Pulmonary artery constriction increased end-diastolic MCL in the free right ventricular wall and reduced end-diastolic MCL and MS in the septum and free left ventricular wall. Thus, the myocardium, including the interventricular septum, is uniformly expanded during saline infusion and pericardiotomy. The interventricular septum behaves as part of the left ventricle during aortic and pulmonary artery constriction. The pericardium imposes a restraint on the interventricular septum and free walls of the ventricles during volume loading, but not during pressure loadings, because dilation of one ventricle is associated with shrinkage of the other.

Effect of Dopamine and Calcium on Lipolysis and Myocardial Ischemic Injury following Acute Coronary Occlusion in the Dog

Ischemic myocardial injury was quantified as the sum of S-T segment elevations in epicardial electrocardiogram recordings (ΣS-T) following acute coronary artery occlusions in 17 dogs. ΣS-T rose from 3 ± 1 mv to 26 ± 4 mv (P < 0.001) following occlusion. Myocardial contractility was similarly stimulated by intravenous infusions of dopamine or calcium. At reocclusions of the coronary artery, ΣS-T increased to 73 ± 12 mv (P < 0.001) with dopamine and to 41 ± 7 mv (P < 0.001) with calcium; the difference was statistically significant (P < 0.005). Arterial concentrations of free fattv acids (FFAa) were raised from 248 ± 33 μEq/liter to 888 ± 161 μEq/liter (P < 0.005) with dopamine, but administration of calcium did not influence FFAa. After inhibition of lipolysis with β-pyridyl carbinol, no difference in ΣS-T or FFAa was observed; the mean values were 31 ± 4 mv for ΣS-T and 144 ± 13 μEq/liter for FFAa. Myocardial lipolysis was suggested in three experiments in which β-pyridyl carbinol reduced ΣS-T with dopamine, although FFAa remained unchanged. These measurements suggest that dopamine-induced lipolysis contributes significantly to the enlargement of ischemic injury in the myocardium following acute coronary artery occlusion, probably due to the metabolic stimulation of myocardial oxygen requirements. Test doses of dopamine given to seven patients raised FFAa by 225 ± 87 μEq/liter (P < 0.03).

Cardiac effects of isoproterenol during graded myocardial ischemia.

Conflicting results of isoproterenol administration to patients with ischemic heart disease suggest that the effect of isoproterenol on cardiac function is related to the severity of myocardial ischemia. Myocardial oxygen consumption (MVO2) was therefore reduced by graded reductions in coronary blood flow before and after coronary administration of isoproterenol in 9 anesthetized dogs. When coronary blood flow was reduced by less than 50 per cent of control value, cardiac output and maximal value of left ventricular pressure rise (dP/dt) were higher with isoproterenol than without at similar values of MVO2. When coronary blood flow was further reduced, however, cardiac output and dP/dt were depressed by isoproterenol. Myocardial lactate production was at any MVO2 value higher during isoproterenol administration than during control periods, and stimulation of myocardial glycolysis by isoproterenol might –- at least in part –- explain an improved cardiac function during moderate ischemia. From these experim...

Cardiac Effects of Nicotine in Dogs

To examine how nicotine increases left ventricular stroke volume despite a concomitant rise in aortic blood pressure, the effects of nicotine and aortic constriction were compared in 11 anesthetized open-chest dogs whose myocardial dimensions were measured by ultrasound elements sewn into the ventricular wall. Stroke volume was increased by 22 ± 7% (mean ± S.E.M.; P < 0.02) during infusion of nicotine (20–25 μg · kg−1 · min−1). Simultaneously, left ventricular end-diastolic pressure (LVEDP) and end-diastolic myocardial chord length (EDMCL) increased (P < 0.005), as did systolic myocardial shortening (MS) (P < 0.01) and myocardial contractility (P < 0.001). Left ventricular systolic pressure (LVSP) rose by 37 ± 5 mm Hg (P < 0.001) during the infusion of nicotine. When a similar increase in LVSP was effected by aortic constriction, stroke volume was reduced by 12 ± 4% (P < 0.01), and LVEDP and EDMCL increased significantly more than during the nicotine infusion, whereas MS and myocardial contractility remai...

Effect of practolol on left ventricular dimensions during coronary occlusion

Beta adrenergic blockade has been suggested to improve the myocardial oxygen balance during ischemic conditions. This investigation was undertaken to examine the effects of practolol, a relatively cardiospecific beta adrenergic blocking agent, on regional myocardial dimensions and shortening during acute coronary arterial occlusion in dogs. Local myocardial dimensions were measured ultrasonically in ischemic and nonischemic regions of the left ventricle. Myocardial dilatation and marked reduction in systolic shortening occurred in ischemic regions after occlusion, whereas nonischemic regions were only moderately dilated. Administration of 10 to 20 mg of practolol exerted different effects in the two ventricular regions; myocardial dilatation was reduced and the systolic shortening increased by practolol in ischemic regions, whereas further dilatation and diminished shortening occurred in nonischemic control regions. Similar results were obtained when heart rate was kept constant by atrial pacing during beta adrenergic blockade. Thus, practolol improved the function in ischemic ventricular regions, and restored ventricular stroke volume to preocclusion levels, probably as a result of improved myocardial oxygen balance.

Effects of Glucagon and Isoproterenol on Severity of Acute Myocardial Ischemic Injury

Comparison was made between the effects of isoproterenol and glucagon on myocardial ischemic injury following acute coronary artery occlusion in 8 dogs. Maximal rate of left ventricular pressure rise (dP/dt) was similarly increased by isoproterenol (63 ± 6 %) (mean ± S.E.M.) and glucagon (65 ± 5 %) infusions. Ischemic injury was measured as the sum of S-T segment elevations in epicardial ECG recordings from 8–10 sites (σST). σST during coronary artery occlusion alone averaged 22 ± 1 mV. Reocclusion of the artery performed during isoproterenol infusion increased σST to 70 ± 7 mV, while during glucagon σST rose to only 51 ± 7 mV. The difference in σST obtained with isoproterenol and glucagon was statistically significant (P < 0.001). Arterial concentrations of free fatty acids (FFAa) were raised from 225 ± 26 to 1213 ± 166 μEq/l by isoproterenol (P < 0.001), whereas glucagon had no significant effect upon FFAa. The experiments were repeated after inhibition of catecholamine-induced lipolysis with β-pyridyl ...

Influence of left ventricular dimensions on endocardial and epicardial qrs amplitude and st segment elevations during acute myocardial ischemia

The influence of acute myocardial ischemia and changes in ventricular dimensions on endocardial and epicardial electrograms were evaluated in 17 anesthetized open-chest dogs before and after left ventricular volume expansion and before and after coronary artery ligation. In eight dogs, regional myocardial blood flow was determined by the labeled microsphere technique. Endocardial QRS (endo-QRS) amplitude in ischemic and nonischemic zones, and epicardial QRS (epi-QRS) in nonischemic zones maintained a negative linear relation with left ventricular end-diastolic dimension before and after coronary artery ligation, although acute ischemia decreased endo-QRS independently. Epi-QRS amplitude in the ischemic zone decreased after coronary artery ligation but changed inconsistently during volume expansion. Ischemia-induced epicardial STsegment elevation decreased during volume expansion and was associated with improved epicardial blood flow. Changes in epi-QRS in ischemic zones, however, were not related to epicardial blood flow during volume expansion. These findings indicate the potential problems of using changes in QRS amplitude for determining the extent of myocardial ischemic injury.