Left Ventricular Failure In Dogs Research Articles

Effect of enalaprilat on splanchnic vascular capacitance during acute ischemic heart failure in dogs

This study investigates the effect of angiotensin-converting-enzyme inhibition by intravenous enalaprilat (100 micrograms/kg) on splanchnic vascular capacitance during acute left ventricular failure induced by coronary microembolization in alpha-chloralose/urethan anesthetized dogs. Changes in hepatic and splenic vascular volumes were determined from organ diameters (sonomicrometry) at 15, 30, and 45 min after enalaprilat injection. Changes in vascular capacitance were assessed from organ pressure-diameter curves obtained during transient hepatic outflow occlusion. Thirty minutes after enalaprilat, hepatic volume was increased by 52 +/- 14 ml (P < 0.01), and portal and hepatic vein pressures were decreased from 10.2 +/- 0.9 to 8.7 +/- 0.8 mmHg (P < 0.01) and from 3.9 +/- 1.6 to 3.1 +/- 0.7 mmHg (P < 0.05), respectively. Splenic volume did not change. Enalaprilat shifted the hepatic pressure-diameter curve upward, resulting in a larger hepatic volume at any given pressure. Curve intercept was increased, suggesting an increase in unstressed vascular volume. Curve slope was unchanged. In conclusion, enalaprilat increased hepatic vascular volume during acute left ventricular failure in dogs. The pressure-diameter curve shift suggests a reduction in the smooth muscle tone of hepatic capacitance vessels.

Left Ventricular Systolic and Diastolic Function during Coronary Arteriography before and after Acute Left Ventricular Failure in Dogs

The hemodynamic side effects of intracoronary injection of low osmolality contrast media were studied in anesthetised dogs, both with and without left ventricular (LV) failure. LV failure was induced by microembolization of the area supplied by the left main coronary artery. LV pressure and volume, aortic pressure, and cardiac output were recorded. 6 ml iodixanol 320 mg I/ml containing 20 mmol Na+/l, a new non-ionic dimer, was compared to iohexol and ioxaglate. Iodixanol induced small systolic alterations both before and after LV failure. Iohexol increased LV inotropy while ioxaglate depressed myocardial function. Before failure iodixanol and ioxaglate impaired isovolumic relaxation, but early diastolic filling was not reduced. After failure the relaxation process was not affected, but ioxaglate reduced early diastolic filling. Ioxaglate also increased LV end-diastolic pressure and volume more than the non-ionic contrast media. In conclusion, iodixanol induced only small changes in systolic and diastolic function. Iodixanol should therefore be hemodynamically well tolerated during coronary arteriography, and also in acute ischemic heart failure.

Left Ventricular Systolic and Diastolic Function during Coronary Arteriography before and after Acute Left Ventricular Failure in Dogs

The hemodynamic side effects of intracoronary injection of low osmolality contrast media were studied in anesthetised dogs, both with and without left ventricular (LV) failure. LV failure was induced by microembolization of the area supplied by the left main coronary artery. LV pressure and volume, aortic pressure, and cardiac output were recorded./6 ml iodixanol 320 mg I/ml/containing 20 mmol Na+/1, a new non-ionic dimer, was compared to iohexol and ioxaglate. Iodixanol induced small systolic alterations both before and after LV failure. Iohexol increased LV inotropy while ioxaglate depressed myocardial function. Before failure iodixanol and ioxaglate impaired isovolumic relaxation, but early diastolic filling was not reduced. after failure the relaxation process was not affected, but ioxaglate reduced early diastolic filling. Ioxaglate also increased LV end-diastolic pressure and volume more than the non-ionic contrast media. in conclusion, iodixanol induced only small changes in systolic and diastolic ...

Class III antiarrhythmic activity of UK-68, 798 in acute ischaemic left ventricular failure in dogs

Class III antiarrhythmic activity of UK-68, 798 in acute ischaemic left ventricular failure in dogs

Haemodynamic effects of a new class III antiarrhythmic drug, [formula omitted], during acute ischaemic left ventricular failure in dogs

Haemodynamic effects of a new class III antiarrhythmic drug, [formula omitted], during acute ischaemic left ventricular failure in dogs

A stable model of acute left ventricular failure in dogs produced by combination of embolization of left coronary artery and infusion of methoxamine: M. Nakazawa, T. Ishihara, Y. Takahashi, M. Okuhira, S. Imai. Department of Pharmacology, Niigata University School of Medicine, Niigata, Japan

A stable model of acute left ventricular failure in dogs produced by combination of embolization of left coronary artery and infusion of methoxamine: M. Nakazawa, T. Ishihara, Y. Takahashi, M. Okuhira, S. Imai. Department of Pharmacology, Niigata University School of Medicine, Niigata, Japan

Cardiovascular effects of positive end-expiratory pressure during acute left ventricular failure in dogs.

Haemodynamic and metabolic effects of ventilation with positive end-expiratory pressure (PEEP) were studied in closed-chest dogs anaesthetized with sodium pentobarbital during normal cardiac function and during acute left ventricular (LV) failure. LV failure was induced by embolizing the left coronary bed with 50 micron plastic microspheres causing a marked depression of LV function. End-expiratory pressure was set to 0, 5, 10 and 15 cm H2O both before and after coronary embolization. During normal cardiac function PEEP above 5 cm H2O depressed cardiac output (CO) significantly. However, following coronary embolization after which LV function was seriously impaired, CO was maintained as PEEP was applied. This is attributed to reduced sensitivity to the LV pre-load reductions induced by PEEP during LV failure. PEEP reduced MBF both during normal and impaired LV function. This did not result in ischaemic myocardial metabolism assessed by lactate extraction either in normal hearts or following coronary embolization. The reduced MBF was, however, associated with reduced MVO2 both during normal cardiac function and during LV failure. It is suggested that the reduced MBF is mainly due to reduced myocardial oxygen demand probably caused by reduced LV wall tension during PEEP ventilation.

Effects of β-Receptor Blockade on Regional Blood Flows During Acute Left Ventricular Failure in Dogs

This study describes the effects of beta-receptor blockade on systemic hemodynamics and regional blood flows during acute ischemic heart failure in dogs. Depression of left ventricular (LV) function was induced by embolization of the left main coronary artery and was evidenced by a significant increase in LV end-diastolic pressure (LVEDP) and decrease in LV dP/dtmax and in cardiac output. Measurements of femoral, renal, mesenteric, and carotid blood flows showed a redistribution of cardiac output during failure. Femoral blood flow decreased to a greater extent than did cardiac output, carotid blood flow decreased in proportion to cardiac output, whereas mesenteric and renal blood flows were moderately reduced in relation to the decrease in cardiac output. Administration of 0.125 mg of propranolol intravenously (i.v.) significantly decreased the performance of the failing left ventricle. Reductions in cardiac output were accompanied by reductions in the peripheral circulations. The decrease in flow was evenly distributed in the femoral, mesenteric, and carotid vascular beds, while there was a relative preservation of renal blood flow. When the dose of propranolol was increased to 0.5 mg/kg, there were no further significant hemodynamic alterations.

Effects of high doses of insulin on regional blood flows during acute left ventricular failure in dogs.

This study describes the effects of high doses of insulin on systemic haemodynamics and regional blood flows during acute ischaemic heart failure in dogs. Left ventricular (LV) dysfunction was induced by embolization of the left main coronary artery, and was evidenced by a significant increase in LV end-diastolic pressure and decrease in LVdP/dtmax and cardiac output. Measurements of femoral, renal, mesenteric and carotid blood flows showed a redistribution of cardiac output during failure. Femoral blood flow decreased to a greater extent than cardiac output, but carotid blood flow decreased in proportion to cardiac output, while mesenteric and renal blood flows were moderately reduced in relation to the decrease in cardiac output. Administration of 300 IU of fast-acting insulin significantly improved the performance of the failing left ventricle. Cardiac output was raised to levels observed before failure. The greatest increases in peripheral flow occurred in the femoral and carotid vascular beds, while the least occurred in the mesenteric and renal vascular beds. These observations indicate that insulin at high dose levels significantly improves peripheral circulation by positive inotropic and vasodilatating effects. There was a tendency to favour femoral and carotid vascular flows, but not at the expense of renal and visceral flows. Beta receptor blockade blocked neither the systemic nor regional haemodynamic effects of insulin.

Haemodynamic effects of insulin and beta receptor blockade during acute left ventricular failure in dogs.

Acute ischaemic heart failure was induced in 13 dogs by coronary embolisation. Severe dysfunction of the left ventricular (LV) performance was shown by a significant increase in LV end-diastolic pressure and significant decreases in maximum rate of LV pressure rise (LVdP/dtmax), stroke volume and cardiac output. 300 IU of fast-acting insulin was injected as a bolus dose in 7 dogs 90 min after the embolisation procedure. This was followed by infusion of glucose and potassium to maintain normal blood levels. After 15 min, insulin had significantly improved the performance of the failing left ventricle. Total peripheral resistance was decreased. Myocardial blood flow was significantly increased while myocardial oxygen consumption was unchanged. After beta receptor blockade with propranolol 0.5 mg kg-1 given intravenously, the improvement in cardiac performance was reduced, heart rate decreased, and a concomitant decrease in myocardial blood flow and oxygen consumption was recorded. Compared with values before treatment, the net effect of combined insulin and beta receptor blockade was unchanged LVdP/dtmax, LV end-diastolic pressure and cardiac output, significantly increased stroke volume and decreased heart rate, and moderately reduced total peripheral resistance and mean aortic blood pressure. Myocardial blood flow was unaltered, while myocardial oxygen consumption was significantly reduced. In the control group of 6 dogs propranolol was given before insulin, and similar haemodynamic alterations were found.

Hemodynamic and Metabolic Effects of Dopamine and Insulin During Acute Left Ventricular Failure in Dogs

Acute ischemic heart failure was induced in eight dogs by coronary embolization. Severe depression of the left ventricular (LV) performance was evidenced. At 15 min after the embolization procedure, dopamine was infused at a dosage sufficient to increase the maximum rate of LV pressure rise (LVdP/dtmax) by approximately 50%. The significant improvement in cardiac performance was obtained at unaltered myocardial oxygen consumption (MVo2). Dopamine infusion was concluded, and after a stabilization period 300 IU of insulin was injected. This was followed by the infusion of glucose and potassium to maintain levels. Insulin significantly improved the performance of the failing left ventricle at unaltered MVo2, but to a lesser extent than did dopamine. Additional dopamine infusion further significantly improved cardiac performance. The net effect of insulin and dopamine in combination as compared with dopamine alone was a significantly greater increase in stroke volume and cardiac output due to a more pronounced decrease in total peripheral resistance. Dopamine increased arterial concentrations and myocardial uptake of free fatty acids (FFA). The net metabolic effect of insulin and dopamine in combination as compared with dopamine alone was a shift in myocardial substrate uptake from FFA to carbohydrates.

Comparative Effects of Dobutamine and Corwin, a β1-Adrenergic Partial Agonist, in Experimental Left Ventricular Failure

Corwin is a new, long-acting beta 1-adrenergic partial agonist for oral and intravenous (i.v.) use. The effects of corwin were compared with those of dobutamine in acute ischemic left ventricular failure in dogs. Failure was produced by embolization of the left main coronary artery with 50 micron plastic microspheres. This induced severe depression in left ventricular function, as evidenced by a marked increase in left ventricular end-diastolic pressure, reduction in left ventricular dP/dtmax, and cardiac output. After 45 min was allowed for stabilization, the 27 dogs were randomly assigned to three groups: control (n = 9), dobutamine-treated (5-10 micrograms/kg/min i.v., n = 9), and corwin-treated (0.025-0.10 mg/kg i.v., n = 9). The doses of dobutamine and corwin were adjusted to give an increase in left ventricular dP/dtmax of 50%. Both drugs similarly increased cardiac output (p less than 0.01), lowered left ventricular end-diastolic pressure (p less than 0.01) and total peripheral vascular resistance (p less than 0.01), but did not affect the heart rate. Only dobutamine increased the mean arterial pressure (p less than 0.01). Both drugs also increased the arterial concentrations and myocardial uptake of fatty acids (p less than 0.05) but caused only a small and nonsignificant increase in myocardial oxygen consumption. Our findings indicate that the hemodynamic and metabolic profiles of corwin and dobutamine are similar, and both drugs should be of special value in the treatment of congestive heart failure. Since corwin can be given orally and has a longer duration of action, it is potentially useful in the long-term treatment of heart failure.

Haemodynamic effects of high doses of insulin during acute left ventricular failure in dogs.

Haemodynamic effects of pharmacological doses of insulin during acute ischaemic heart failure were studied in 8 dogs. Severe depression of left ventricular function was induced by the injection of 50 micron plastic microspheres into the left main coronary artery. This was demonstrated by a significant increase in left ventricular end-diastolic pressure and a significant decrease in the maximum rate of left ventricular pressure rise (LVdP/dtmax), stroke volume and cardiac output. Eighty-five minutes after the embolization procedure, 300 IU of insulin free of glucagon and calcium was injected as a bolus. This was followed by infusion of glucose and potassium to maintain physiological levels of these factors. Five minutes after insulin administration, there was a significant improvement in left ventricular performance as shown by decreased left ventricular end-diastolic pressure (P less than 0.01) and increased LVdP/dtmax (P less than 0.01), stroke volume (P less than 0.05) and cardiac output (P less than 0.05). A significant reduction in heart rate occurred. A non-significant increase in mean aortic blood pressure and reduction in total peripheral resistance were seen. In conclusion, pharmacological doses of insulin significantly improve cardiac pump function during acute ischaemic left ventricular failure in dogs.

Metabolic effects of high doses of insulin during acute left ventricular failure in dogs.

Metabolic effects of pharmacological doses of insulin were studied during acute ischaemic heart failure in 7 dogs. Severe depression of left ventricular performance was induced by embolization of the left main coronary artery with 50 micron plastic microspheres. This was followed by a significant reduction in myocardial blood flow and oxygen consumption. After a period of stabilization of the haemodynamic and metabolic variables, 300 IU of insulin free of glucagon and calcium was injected as a bolus dose. Glucose and potassium were given to maintain their plasma concentrations. Insulin significantly improved performance of the failing left ventricle. Myocardial blood flow was significantly increased, whereas myocardial oxygen consumption was unchanged. Insulin significantly reduced arterial concentrations and myocardial uptake of free fatty acids, while myocardial uptake of glucose and lactate showed a non-significant increase. In conclusion, pharmacological doses of insulin significantly improve cardiac pump function without increasing myocardial oxygen consumption during acute ischaemic left ventricular failure in dogs. This may be partly related to reduced myocardial uptake of free fatty acids relative to that of glucose.

Functional and metabolic effects of dopamine and high dose insulin during acute left ventricular failure in dogs

Functional and metabolic effects of dopamine and high dose insulin during acute left ventricular failure in dogs

Haemodynamic and metabolic consequences of elevated plasma free fatty acids during acute ischaemic left ventricular failure in dogs.

Haemodynamic and metabolic effects of elevated plasma concentrations of free fatty acids (FFA) were studied during acute ischaemic left ventricular failure in closed-chest anaesthetized dogs. Embolization of the left main coronary artery with 50 micron plastic microspheres induced severe depression of left ventricular performance as indicated by a marked increase in left ventricular end-diastolic pressure (LVEDP), and marked reductions in LVdP/dtmax, cardiac output and myocardial oxygen consumption (MVO2). When stable conditions were reached, eight dogs received a triglyceride emulsion and heparin to raise plasma FFA. This was associated with increased MVO2 and further elevation of LVEDP. In two dogs receiving the triglyceride emulsion but no heparin, plasma FFA was not elevated, and MVO2 and LVEDP were unchanged. In conclusion, elevation of plasma FFA was associated with increased myocardial oxygen requirement and further depression of LV function in dogs with acute ischaemic LV failure.

Ventricular diastolic pressure-volume shifts during acute ischemic left ventricular failure in dogs

Ischemic left ventricular failure was produced in eight acutely instrumented, anesthetized dogs to study the contribution of changing myocardial compliance and pericardial pressure to shifts in right and left ventricular diastolic pressure-volume relations. Right and left ventricular and pericardial volumes were measured by ungated computed tomography. Cardiac volumes were manipulated by infusion of saline solution, hemorrhage, phenylephrine infusion and, during failure only, nitroglycerin administration. During both control and failure periods, these interventions shifted the left and right ventricular pressure-volume relations by changing pericardial pressure only; that is, these interventions caused no change in the ventricular transmural pressure-volume relation. The induction of failure as such increased pericardial pressure only minimally and did not change the left ventricular or right ventricular transmural pressure-volume relations significantly. Volume loading during the control period caused an apparent pericardial creep which attenuated the pericardial effect on ventricular pressure-volume relations. During failure, volume loading caused an increase of right ventricular volume, but tended to decrease left ventricular volume; this was associated with a leftward displacement of the interventricular septum. In conclusion, in the presence of ischemic left ventricular failure as well as normally, changes in preload, afterload and circulating blood volume shift ventricular diastolic pressure-volume relations by stretching or relaxing the pericardium, thus changing pericardial pressure. In these circumstances, there were no consistent changes in myocardial compliance.

Haemodynamic and metabolic consequences of elevated plasma free fatty acids during acute ischaemic left ventricular failure in dogs

Haemodynamic and metabolic effects of elevated plasma concentrations of free fatty acids (FFA) were studied during acute ischaemic left ventricular failure in closed-chest anaesthetized dogs. Embolization of the left main coronary artery with 50 micron plastic microspheres induced severe depression of left ventricular performance as indicated by a marked increase in left ventricular end-diastolic pressure (LVEDP), and marked reductions in LVdP/dtmax, cardiac output and myocardial oxygen consumption (MVO2). When stable conditions were reached, eight dogs received a triglyceride emulsion and heparin to raise plasma FFA. This was associated with increased MVO2 and further elevation of LVEDP. In two dogs receiving the triglyceride emulsion but no heparin, plasma FFA was not elevated, and MVO2 and LVEDP were unchanged. In conclusion, elevation of plasma FFA was associated with increased myocardial oxygen requirement and further depression of LV function in dogs with acute ischaemic LV failure.

Effects of a new angiotensin converting enzyme inhibitor, enalapril, in acute and chronic left ventricular failure in dogs.

Enalapril (MK-421) is a new angiotensin converting enzyme inhibitor which effectively lowers elevated blood pressure and might also be useful in heart failure. Enalapril was infused into six awake dogs 2 hours after left circumflex coronary artery embolization (acute failure group) and into six other awake dogs two to six months after coronary embolization (chronic failure group). In the acute failure group 2 hours after embolization, increased left ventricular end-diastolic pressure and reduced cardiac output remained unchanged during enalapril infusion. In the chronic failure group, increased left ventricular end-diastolic pressure also remained unchanged during enalapril infusion, but cardiac output, which had fallen to 131.8 +/- 11.9 (S.D.) from 165.8 +/- 17.9 ml/min/kg (P less than 0.01) by two to six months in this group rose during enalapril infusion to 154.5 +/- 27.7 ml/min/kg (P less than 0.05). Heart rate and blood pressure were not changed during enalapril in either group, but stroke volume rose (26.0 +/- 5.9 to 29.2 +/- 6.9 ml, P less than 0.01) and systemic vascular resistance fell (58.5 +/- 10.3 to 39.3 +/- 4.3 units, P less than 0.01) during enalapril only in the chronic failure group. Plasma renin activity after embolization was slightly but not significantly higher in the acute failure group. Thus, enalapril appears to be an arterial vasodilator in dogs with chronic but not acute left ventricular failure.

Inosine infusion in dogs with acute ischaemic left ventricular failure: favourable effects on myocardial performance and metabolism.

Haemodynamic and metabolic effects of inosine were examined during acute left ventricular (LV) failure in closed-chest anaesthetised dogs. Embolisation of the left main coronary artery with 50 microm plastic microspheres induced severe depression of LV function, and the dogs remained in stable failure throughout the experimental period as shown in the untreated control dogs (n = 4). Intravenous infusion of inosine 3.8 to 7.5 mg . min-1 . kg-1 caused an increase in maximum LVdP/dt from 290 +/- 32 (mean +/- SEM, n = 8) to 376 +/- 39 kPa . s-1 and a decrease in LV end-diastolic pressure from 3.6 +/- 0.2 to 2.5 +/- 0.1 kPa. Total peripheral resistance decreased from 10.2 +/- 1.0 to 7.4 +/- 0.7 kPa . litre-1 min, and cardiac output increased from 1.64 +/- 0.17 to 2.27 +/- 0.23 litre . min-1 during inosine infusion. Myocardial blood flow increased from 65 +/- 10 to 94 +/- 16 cm3 . min-1 . 100 g-1 with no change in myocardial oxygen consumption. Inosine markedly decreased arterial concentrations and myocardial uptake of FFA. Arterial concentrations of glucose were moderately decreased while myocardial uptake of glucose showed a non-significant increase. Inosine markedly increased myocardial uptake of lactate. These metabolic changes were associated with increased plasma concentrations of insulin. In conclusion, inosine improved myocardial performance and increased myocardial uptake of carbohydrates relative to FFA during acute ischaemic LV failure in dogs.