Increase In Mean Aortic Pressure Research Articles

Metabolic and cardiovascular changes during physical restrains in rats.

When conscious rats were physically restrained, their body temperature, heart rate and heat production increased within minutes. The rate of increase in heat production was less than that in heart rate, particularly in warm environments. Reduction of oxygen pulse, consequently either stroke volume or (A-V) O2 difference, was suggested. Stroke volume cardiac output and its fractional distribution to most of the calorigenic organs measured by the reference sample method using 85Sr-labelled microspheres decreased significantly by restraint. However, fractional distribution of cardiac output increased greatly to the skeletal muscles. The restraint-hypermetabolism may be attributed to the increased metabolism of the skeletal muscles supported with an increased availability of oxygen. With a slight increase in mean aortic pressure, total peripheral resistance increased greatly as observed during Valsalva-like maneuver. The decrease in cardiac output and stroke volume during restraint may be caused by obstruction to the systemic venous return.

Increased adenosine formation by rat myocardium with acute aortic constriction

Based primarily on the observations that adenosine release by the heart is inversely related to oxygen supply to the myocardium, it has been proposed that adenosine serves as a metabolic regulator of coronary vascular resistance. The present study was undertaken to determine to what extent adenosine formation is influenced by increases in mean aortic pressure, which is known to elevate myocardial oxygen requirements. In pentobarbital-anesthetized rats, aortic pressure and aortic blood flow were measured during control periods and during constriction of the thoracic aorta. The hearts were frozen in situ and assayed for adenosine and its breakdown products, inosine and hypoxanthine. In a control group of 16 rats, cardiac adenosine levels were 3.6±0.2 nmol/g tissue. In a second group of seven rats, aortic constriction elevated aortic pressure by 108% without a reduction in cardiac output, and tissue adenosine levels were 5.6±0.8 nmol/g ( P < 0.005). The experimental group also demonstrated an increase in the sum of hypoxanthine, inosine and adenosine from 8.2±0.8 nmol/g observed in controls to 17.2±1.7 nmol/g ( P < 0.001). In contrast, no significant difference was observed in adenosine, inosine and hypoxanthine contents of hearts allowed to recover after release of aortic constriction compared to hearts in parallel time-control experiments. These results suggest a direct relationship between myocardial oxygen consumption and the formation of adenosine during acute aortic constriction.

Interaction of aortic pressure and left ventricular end-diastolic pressure in the dog.

Fiber length (preload) is an important determinant of left ventricular performance. Mean aortic blood pressure also influences ventricular performance. The present study was undertaken to examine the influence of mean aortic pressure on the fiber length-ventricular performance relationship. Fifteen anesthetized, adrenergically blocked dogs were studied on right-heart bypass at constant heart rate and coronary blood flow. An increase in mean aortic pressure permitted a greater improvement in performance as evaluated by stroke work for a given increase in left ventricular end-diastolic pressure. A given increase in mean aortic pressure at a constant stroke volume produced a greater rise in stroke work over intermediate ranges of left ventricular end-diastolic pressure than occurred with higher or lower left ventricular end-diastolic pressure. Thus, the degree of afterload-induced performance improvement depended on the magnitude of the preload. External circumference-left ventricular end-diastolic pressure data suggested a possible relationship between isovolumic systolic circumferential expansion and the improvement of ventricular performance at higher mean aortic pressures.

Comparison of dobutamine and dopamine in treatment of severe heart failure.

The haemodynamic effects of dobutamine, a new synthetic catecholamine, were studied in 12 patients with severe congestive heart failure and compared with those of dopamine in 10 clinically similar patients. Dobutamine produced a distinct increase in cardiac index, while lowering left ventricular end-diastolic pressure and leaving mean aortic pressure unchanged. Dopamine also significantly improved cardiac index, but at the expense of a greater increase in heart rate than occurred with dobutamine. Dopamine was ineffective in lowering left ventricular end-diastolic pressure, but increased mean aortic pressure. We conclude that dobutamine is an effective, positive inotropic agent in patients with severe congestive heart failure. Because it has comparatively little effect on heart rate and aortic pressure, both major determinants of myocardial oxygen consumption, it may be of special value in patients with the low output syndrome associated with coronary heart disease.

CARDIOVASCULAR RESPONSES TO INTRAVENTRICULAR HEMORRHAGE IN NEONATAL PIGLETS

In view of the prevalence of intraventricular hemorrhage (IVII) as a cause of neonatal demise, the cardiovascular responses to experimental IVII were studied. 18 piglets ranging in age from birth to 16 days were anesthetized with 0.25% halothane in an H2O-O2 mixture and artificially ventilated. Blood gas parameters were controlled. Aortic pressure (AoP), spinal fluid pressure (SFP), heart rate (HR), and femoral, renal and carotid flows were recorded continuously. IVH was simulated by serial injections of 0.5 ml of blood into the right lateral ventricle. Norepinephrine was used to test responsiveness of peripheral receptors. Age-dependency of effects was evaluated statistically for all parameters. A total of 4.0 ml IVH with at least 70% increase in SFP led to a maximum of 59% increased mean AoP; and 50% increased HR in all piglets younger than 5 days of ane. Renal resistance (R) increased at all ages but femoral R did not. Carotid R increased 16.0%±3.9 in animals 4 days old or less and 49.6%±10.4 in one week old animals. Immaturity of the cardiovascular regulatory system was apparent as an absence of the adult pattern of response to increased SFP during IVH in the piglets. There was a precipitous fall in cardiovascular parameters just before the demise of the animal resembling that seen in terminal infants.

Inotropic and chronotropic responses of the in vivo denervated dog myocardium to dobutamine.

The inotropic and chronotropic responses to dobutamine (DBA) and isoprenaline (5ISO) were examined in eight chloralose anaesthetised dogs. Following acute cardiac denervation, heart rate (HR) and contractility (dP/dtmax), measured at a fixed paced atrial rate, were recorded during intravenous infusion of incremental doses of DBA and ISO. Both DBA and ISO elicited increases in HR and dP/dtmax. The increases in dP/dtmax for a one beat per minute increase in HR was 102.0 +/- 10.6 mm Hg/s (1 mm Hg (0 degree C) = 133.322 Pa), during DBA infusion, and 61.5 +/- 8.4 mm Hg/s during ISO infusion. It appeared that the relatively greater inotropic effect of DBA in comparison with ISO was the result of an augmentation of its inotropic activity. DBA infusion was accompanied by a significant increase in mean aortic pressure at all doses examined. An increase in afterload may account for part of the increased inotropic responses to DBA.

Comparative systemic and regional hemodynamic effects of dopamine and dobutamine

Dopamine and dobutamine are sympathomimetic amines with divergent peripheral vascular actions. The renal, mesenteric, and femoral vascular and total systemic hemodynamic effects of these amines were compared in pentobarbital-anesthetized dogs. Both agents increased myocardial contractility. Infusion rates of dopamine greater than 5 μg per kilogram per minute increased mean aortic pressure. Dobutamine increased the systolic pressure but did not alter mean aortic pressure. Dobutamine increased cardiac output more than dopamine. Dopamine infusions up to 10 μg per kilogram per minute increased renal and mesenteric blood flow and decreased vascular resistance. Dobutamine had negligible effects on the renal or mesenteric blood flow but produced dose-related increases in femoral blood flow. Dopamine did not significantly alter femoral hemodynamics. These results more clearly define the systemic and regional vascular hemodynamic effects of these agents.

Effect of hypoxia on vascular responses to the carotid baroreflex.

The effect of systemic hypoxia on the vascular responses to the carotid baroreflex was studied in anesthetized, vagotomized, artificially ventilated dogs. One hindlimb, kidney, gracilis muscle, and paw were perfused at constant flow, and neurograms were obtained from renal sympathetic fibers. Bilateral carotid occlusions were performed while the animal was breathing a mixture of air and O2 (mean arterial PO2 = 106 mmHg) and again during ventilation with 10% O2 (PO2 = 40 mmHg). With occlusion, the average increase in mean aortic pressure was 36 mmHg greater during hypoxia than during normoxia and the increase in renal perfusion pressure was 87 mmHg greater; the increase in hindlimb perfusion pressure was identical in both situations. Hypoxia did not change the reflex response of the paw to carotid occlusion and increased that of the muscle vessels by only 10%; the increase in renal sympathetic activity averaged 56 plus or minus 10% more with hypoxia than with normoxia. When the carotid chemoreceptors were destroyed, the greater increase in aortic and renal pressure response to carotid occlusion during hypoxia as compared to normoxia was abolished. Thus systemic hypoxia markedly potentiates the reflex renal constriction caused by the baroreflex, and this effect is due to the carotid chemoreceptor afferent input.

Systemic and renal hemodynamic effects of dopamine and prostaglandin A alone and in combination.

Prostaglandin A (PGA) compounds infused intravenously at rates of 0.125, 0.25 and 0.50 &lt;i&gt;µ&lt;/i&gt;g/kg/min decreased mean aortic pressure and renal vascular resistance, but did not increase renal blood flow in pentobarbital-anesthetized dogs. In contrast, dopamine increased renal blood flow at infusion rates of 2.5, 5.0 and 7.5 &lt;i&gt;µ&lt;/i&gt;g/kg/min and increased mean aortic pressure at infusion rates of 5.0 and 7.5 &lt;i&gt;µ&lt;/i&gt;g/kg/min. With simultaneous infusions of PGA (0.125 and 0.25 &lt;i&gt;µ&lt;/i&gt;g/kg/min) and dopamine (2.5, 5.0 and 7.5 &lt;i&gt;µ&lt;/i&gt;g/kg/min), mean aortic pressure decreased and renal blood flow increased. In open-chest dogs, cardiac contractile force was increased more by dopamine than by PGA. Neither agent alone altered heart rate, but when administered together, heart rate increased. PGA (0.01–0.02 &lt;i&gt;µ&lt;/i&gt;g/kg/min) abolished the increase in blood pressure produced by larger doses of dopamine (15–20 &lt;i&gt;µ&lt;/i&gt;g/kg/min) without reducing the increase in renal blood flow. Thus, by varying infusion rates of dopamine and PGA, renal blood flow may be increased with no change, an increase or a decrease in arterial pressure.

Principle defects which account for shock following acute myocardial infarction in man: implications for treatment.

Shock following acute myocardial infarction is closely related to the volume of damaged myocardium. For this reason, the main therapeutic effort should be directed towards improvement of myocardial oxygenation rather than improvement of cardiac performance. Hemodynamics and cardiac energetics were studied in 25 patients in myocardial infarction shock. Hemodynamic abnormalities associated with shock were emphasized when compared to data from 40 patients with acute myocardial infarction but not in shock. Isoproterenol increased cardiac index an average of 0.87 1/min/M2 and heart rate by 20 beats/min; coronary blood flow rose an average of 12 ml/100g/min in face of decreased diastolic aortic (coronary perfusion) pressure; rate of myocardial lactate production increased. L-norepinephrine increased mean aortic pressure and coronary blood flow an average of 21 mm Hg and 27 ml/100g/min; mean myocardial oxygen consumption rose 2.24 ml/100g/min; myocardial lactate production shifted to extraction (mean, 12%); myocardial oxygen extraction remained abnormally high (mean, 73%); cardiac index did not change. Intra-aortic counterpulsation in-creased mean aortic pressure and coronary blood flow an average of 14 mm Hg and 23 ml/100g/ min; myocardial oxygen consumption remained essentially unchanged; both myocardial lactate and oxygen extraction improved toward normal values (15% and 61%); cardiac index in-creased an average of 0.48 1/min/M2. Isoproterenol appears to be harmful in myocardial infarction shock in that it increased myocardial oxygen demand more than oxygen supply. L-norepinephrine seems to be the vasoactive agent of choice in the initial treatment of shock because it improved myocardial perfusion and metabolism but not cardiac index. Intra-aortic counterpulsation improved both coronary and peripheral circulation and the myocardial metabolism changed towards normal. Mortality remained unchanged during the three different therapeutic interventions; emphasizing the importance of early recognition of the pre-shock state and of further aggressive diagnositc and therapeutic measures.

Ouabain induced primary coronary vasoconstriction. 1.

SummaryGiven intravenously, ouabain decreased heart rate and cardiac output and increased mean aortic pressure, stroke volume, total systemic resistance, and mean and late diastolic coronary resistance. Given directly into the coronary circulation, it decreased coronary blood flow and stroke coronary blood flow, increased mean and late diastolic coronary resistance, and produced no systemic effects. This indicated a direct effect on the coronary vasculature. This direct action on the coronary vessels implies possible intensified myocardial damage if administered to an already ischemic heart.

Cardiac performance and metabolism in shock due to acute myocardial infarction in man: response to catecholomines and mechanical cardiac assist.

SummarySystemic hemodynamics and myocardial metabolism were studied in 21 patients in shock due to acute myocardial infarction. The response to isoproterenol was determined in six, to l‐norepinephrine in eight, and to intra‐aortic counterpulsation in 10 patients. Before treatment, cardiac index was markedly reduced, averaging 1.35 L/min/m2. Mean aortic pressures ranged between 40 and 65 mm Hg, while systemic vascular resistance varied widely, averaging 1,575 dynes‐sec‐cm−5. Decreases in coronary blood flow (mean 68 ml/100 g/min) and in myocardial oxygen consumption (mean 8.11 ml/100 g/min) were associated with abnormally high myocardial oxygen extraction (mean 78%) and with lactate production (mean 9%). Isoproterenol increased cardiac index and heart rate an average of 0.85 L/min/m2 and 25 beats/min. Coronary blood flow rose an average of 12 ml/100 g/min in face of unchanged mean aortic pressure, while diastolic aortic pressure fell uniformly. Myocardial lactate metabolism deteriorated. L‐norepinephrine increased mean aortic pressure and coronary blood flow an average of 21 mm Hg and 27 ml/100 g/min. Mean myocardial oxygen consumption rose 2.24 ml/100 g/min. While myocardial lactate production shifted to extraction (mean 12%), myocardial oxygen extraction remained abnormally high (mean 73%). Cardiac index did not improve. Intra‐aortic counterpulsation increased mean aortic pressure and coronary blood flow an average of 15 mm Hg and 23 ml/100 g/min. Myocardial oxygen consumption remained essentially unchanged. Both myocardial lactate and oxygen extraction improved towards normal values (mean 15% and 61%). Cardiac index increased an average of 0.45 L/min/m2. Conclusion: Hemodynamics and myocardial metabolism were markedly abnormal in shock due to acute myocardial infarction. Isoproterenol improved cardiac performance, but myocardial oxygenation deteriorated. Therefore, isoproterenol does not seem to be helpful in coronary shock. L‐norepinephrine improved myocardial perfusion and oxygenation, while cardiac output remained unchanged. Nevertheless, l‐norepinephrine appears to be the vasoactive agent of choice in the initial treatment of coronary shock. Intra‐aortic counterpulsation changed myocardial metabolism towards normal and improved systemic perfusion. Mortality remained unchanged, however, during the three different therapeutic interventions, emphasizing the importance of early recognition of the shock state and of further aggressive diagnostic and therapeutic management.

Regional myocardial blood flow in the dog studied with radioactive microspheres.

Regional myocardial blood flow was studied in the anaesthetized dog by determining the distribution of 15 and 50μ radioactive microspheres after left atrial injection. Doses of the 15μ spheres below 4 × 106 did not significantly alter coronary or systemic haemodynamics. Larger doses produced a significant increase in mean aortic pressure. Less than 1% of the 15μ spheres delivered to the heart passed into the coronary sinus. The myocardial distribution of 15 and 50μ spheres was not significantly different except for the ratio of left ventricular endocardium to epicardium (1·12 for 15μ and 1·45 for 50μ, P<0.001). Using 15μ spheres, it was found that the ratio of endocardial to epicardial radioactivity in the left ventricular wall was increased by propranolol, decreased by isoprenaline, and unchanged by nitroglycerin.

Some aspects of interaction between diphenylhydantoin and digoxin by simultaneous administration to dogs

Diphenylhydantoin, 1.1 mg/kg/min, and digoxin, 2.78 μg/kg/min, were infused separately and simultaneously in anesthetized dogs. Diphenylhydantoin lowered mean arterial pressure and heart rate after 30–40 min of infusion. Its average lethal dose was 127 mg/kg. All animals died in cardiac arrest. The hypotensive effect of diphenylhydantoin was associated with a decrease in cardiac output, stroke volume, peripheral vascular resistance, and maximum left ventricular dp dt . Diphenylhydantoin increased mean right atrial and left ventricular end-diastolic pressures. Digoxin, 2.78 μg/kg/min, infused for 40 min, increased mean aortic pressure, peripheral vascular resistance, and maximum left ventricular dp dt . It decreased cardiac output and heart rate. After 20–30 min of infusion, digoxin caused the usual ECG effects of digitalis: A-V block, premature beats, and paroxysmal ventricular tachycardia. The average lethal dose of digoxin was 0.26 mg/kg. All animals died in ventricular fibrillation. Digoxin given simultaneously with diphenylhydantoin protected animals from diphenylhydantoin-induced hypotension and myocardial depression. The decrease in mean aortic pressure, cardiac output, stroke volume, total peripheral vascular resistance, and maximum left ventricular dp dt as well as the increase in the left ventricular end-diastolic pressure after diphenylhydantoin and digoxin were less pronounced than after diphenylhydantoin alone. Digoxin did not antagonize diphenylhydantoin-induced cardiac slowing. The peripheral vasoconstrictor as well as the positive inotropic effects of digoxin are thought to be responsible for the protection of animals from the diphenylhydantoin-induced hypotension. Diphenylhydantoin, in the doses employed, prevented digoxin-induced elevation of mean arterial pressure, peripheral vascular resistance and maximum left ventricular dp dt ; it increased the dose of digoxin which caused ventricular arrhythmias but had no significant effect on the lethal dose of digoxin. Most animals which received both drugs, died in sudden cardiac arrest, which occurred at a time when the mean arterial pressure was only slightly decreased.

Studies in cardiac necrosis: II. Cardiovascular effects of sympathomimetic amines producing cardiac lesions

The purpose of this study was to determine the mechanisms by which lesion-producing doses of some representative sympathomimetic amines could cause impairment of myocardial function. Impairment of myocardial function was indicated when the aortic outflow was significantly lowered by lesion-producing doses of all the test drugs. The probable mechanisms of impairment differed among the drugs, thus confirming the pluricausal origin of drug-induced myocardial necrosis. Three mechanisms for impairment of function are proposed. Ephedrine, methoxamine, and norephedrine acted through a myogenic mechanism manifested as a reduction in myocardial contractile force. Nordefrin and norepinephrine acted through a physical mechanism by causing an increase in mean aortic pressure which opposed left ventricular pressure. Isoproterenol probably acted by a third mechanism which is believed to be at the level of myocardial utilization of substrate.