Drop In Cardiac Output Research Articles

Anaphylatoxin-induced shock and two patterns of anaphylactic shock: hemodynamics and mediators.

In the dog, different cardiorespiratory reactions were identified in two types of anaphylactic shock and in C5a-AT (anaphylatoxin)-induced shock. All three types had in common a portal blood pooling with consequent decrease in the venous return, cardiac output, and arterial pressure. In anaphylaxis (a) of the first type, at a low titer of hemagglutinating antibodies, the latent period was 68 s and heart and lung function was unchanged. In the second type, at high titer, the latency was 19 s and pulmonary hypertension and decreased heart contractility occurred. After AT injection pulmonary hypertension appeared with tachypnea and unchanged heart function. Tachyphylaxis, but not cross-over tachyphylaxis against the anaphylactic agent and AT was observed in dogs and isolated guinea pig lungs. AT induced a transient release and a, a prolonged release of histamine, prostaglandins (PGs), and thromboxane A2 and endoperoxides from guinea pig lungs. SRS-A was released only in a. Indomethacin inhibited AT-induced release of PGs in guinea-pig lungs and AT-induced hypotension in the dog though it did not prevent the drop in cardiac output. These model studies suggest that different patterns of clinical a. can occur, depending on the type of antibodies and/or mediators involved.

85 CARDIOVASCULAR AND RENAL EFFECTS OF INDOMETHACIN IN NEWBORN DOGS

The cardiovascular effects of indomethacin were studied acutely in 9 newborn dogs (2-32 days) using the radioactive microsphere reference organ technique. Indomethacin, 0.3 mg/kg intravenously, produced a 22% drop in cardiac output (CO) from 224±31* to 175±26 ml/kg/min (p<.05). Renal blood flow fell slightly from 1.6±.2* to 1.3±.2 ml/gm/min (p<.05). Renal inner cortical (IC) and outer cortical (OC) blood flow both fell (p<.01), but did so proportionately with no resultant change in IC/OC ratio. There were no changes in blood flow to the GI tract, heart or lungs. Of particular interest is that although in animals over 7 days (n=5) indomethacin produced no change in cerebral blood flow (CBF), in 2-day-old puppies (n=3) it produced a 47% fall in CBF (p<.05). Indomethacin produced no significant changes in glomerular filtration rate or potassium excretion, but there was a transient drop in tubular sodium reabsorption (p<.01) which rapidly returned to control values after 1½ hours. In summary, indomethacin in a dose currently being used clinically causes small, but statistically significant decreases in CO and renal blood flow, with minimal changes in renal function. However, in very young animals, this dose of indomethacin results in a marked drop in cerebral blood flow not found in older animals.

Myocardial blood flow in the diving seal.

Grey seals exhibit a marked drop in heart rate, a slight decrease in ventricular contractility, and an essentially unchanged stroke volume upon diving. In the present study, we have demonstrated that the resulting drop in cardiac output is associated with a 90% reduction of coronary blood flow. Such reduction of myocardial blood flow takes place despite a significant increase in effective coronary driving pressure, and is indicative of a 800% increase in coronary vascular resistance. This means that the circulatory adjustments displayed by the diving seal (i.e. a reduction of the workload on the heart) are so effective that myocardial blood flow can be reduced to 10% of the pre-dive value without loss of cardiac function and blood pressure. It is suggested that even partial simulation of such a circulatory state might be a successful approach in the treatment of ischemic injuries in the heart of man.

The effect of phenobarbital on asphyxia in the newborn monkey.

This study characterizes the circulatory changes associated with asphyxia in the newborn monkey and examines the effect of phenobarbital on asphyxia. The time to last gasp and duration of total asphyxia as well as heart rate at the start of resuscitation were the same in the phenobarbital-treated and untreated infants. Initial cardiac output was the same in both groups; there was a profound drop in cardiac output with asphyxia which was the same in both groups. Organs which preferentially receive a greater percentage of cardiac output during asphyxia are heart, total brain, and adrenal glands. Organs receiving a decreased percentage of cardiac output during asphyxia are kidneys, liver, and gastrointestinal tract. Cerebral hemisphere flow as a percentage of cardiac output is maintained during asphyxia, whereas paleoencephalon flow as a percentage of cardiac output increases significantly. These data confirm the circulatory redistribution of cardiac output in response to asphyxia described previously in the monkey fetus. The treated infants did not show the prolongation of time to last gasp reported in the monkey fetus; the dose of phenobarbital we used, although adequate to produce sedation, may have been too low to demonstrate the protective effect.

Operant conditioning of heart rate in curarized rats: hemodynamic changes.

Three groups of curarized rats were subjected to operant heart rate conditioning with use of a shock-avoidance procedure while cardiac output, mean arterial pressure, and total peripheral resistance were measured. Heart rate changes in the control group remained constant during the entire 90-min experimental period, while cardiac output decreased significantly. Those rats that were reinforced for increasing their heart rate had a small but statistically significant increase in heart rate, but cardiac output decreased to approximately the same extent as in the control group. The group reinforced for decreasing their heart rate demonstrated a large, significant decrease in heart rate and an even larger drop in cardiac output, which was significantly greater than that of either of the other two groups. Operant conditioning of a single facet of the cardiovascular system resulted in significantly larger changes in other cardiovascular parameters, which may have been partly masked by the physiological effects of d-tubocurarine. Therefore, only when these other measures of cardiovascular function are taken into consideration can interpretation of operant heart rate conditioning become meaningful.

Protection from ischemic cardiac arrest by coronary perfusion with cold Ringer’s lactate solution

Cardiac output, peak systolic pressure, and heart rate were reduced and left ventricular end-diastolic pressure was increased in 10 animals following 1 hour of normothermic aortic cross-clamping. Although no cardiotonic drugs were required for resuscitation, the central venous pressure had to be doubled to achieve preoperative levels of cardiac output and peak systolic pressure. Histologic and hislochemical studies revealed irregular, diffuse damage of 50 per cent of the myocardium. While it is usually assumed that the dog tolerates ischemic cardiac arrest very poorly, this study would indicate that the canine and human hearts do not differ significantly in their tolerance to ischemia, with over 90 per cent of either species surviving 1 hour of normothermic ischemic arrest in spite of serious myocardial damage. On the other hand, in 10 animals whose hearts were cooled by a single aortic root infusion of 4° C. Ringer’s lactate, there was no drop in cardiac output, peak systolic pressure, and heart rate following recovery from 1 hour of ischemic arrest. Histologic and histochemical studies revealed only minimal changes. Profound myocardial hypothermia is easy to achieve by perfusion and protects the myocardium from ischemic damage while providing operating conditions equally as good as with normothermic arrest. To extend the period of ischemic arrest during which no diminution of cardiac function occurs and to reduce myocardial irritability, studies of metabolic inhibitors and hypothermic perfusion solutions without lactate are now in progress.

The hemodynamic effects of practolol in experimental myocardial infarction.

In order to study the circulatory effects of practolol in the depressed heart, myocardial infarction was produced in eight dogs by ligation of multiple coronary artery branches. Significant decreases in cardiac output, stroke volume, and left ventricular dp/dt, concomitant increases in systemic vascular resistance and left ventricular end-diastolic pressure occurred following ligation. The thoracic cavity was closed and the animals were allowed to stabilize their circulatory parameters. Practolol was then given in intravenous doses of 250, 500 and 1,000 µg/kg. These doses resulted in blood levels of 0.18, 0.30 and 0.62 µg/ml, without producing further deterioration of any of the hemodynamic variables that had been depressed by multiple coronary ligation. There was, however, a significant decrease in heart rate without a drop in cardiac output, which resulted in a slight but significant rise in stroke volume following practolol administration. Thus, it is concluded that practolol did not further reduce an already compromised heart in this model of acute infarction.

Hemodynamic effects of pericardial tamponade.

Discussion and conclusionsThe increase in pericardial and central venous pressures is sufficient to impede venous return to the right atrium and thereby produces a striking drop in cardiac output (Fig. 2). In addition there is a moderate reduction in heart rate during the first 15 minutes of the tamponade (Fig. 2), which also contributes to the reduction in cardiac output. Despite the increase in total peripheral resistance, the reduced blood flow results in an immediate and marked drop in arterial pressure. This decrease activates the baroreceptor mechanisms producing an increase in heart rate which eventually exceeds the control values. The oxygen consumption drops initially because of the reduced blood flow but recovers during the course of the experiment almost to the control value. Since the recovery of oxygen consumption was greater than that of the cardiac output, the oxygen extraction from the blood must have increased, especially in the constant pressure experiments. Coincident with the onset of ...

CARDIOVASCULAR RESPONSE TO ACUTE HYPOCAPNIA DUE TO OVERBREATHING.

Anesthetized dogs were maintained by artificial respiration at a fixed rate and depth. The composition of inspired CO2 was varied while O2 content was maintained at control levels. Cardiac output was measured by the indicator-dilution technique. Acute reduction of end-expiratory CO2 levels below the normal value caused a decrease in blood pressure, pulse pressure, stroke volume, and cardiac output, no essential change in heart rate and an increase in total peripheral resistance. Mean systemic blood pressure and net vascular resistance were less with hypocapnia than they were at the same cardiac output at normal CO2 levels. However, the over-all vascular resistance was greater with hypocapnia than it was in the same animal at normal CO2 levels and control output values. Analysis of these data leads to the conclusion that the hypocapnia produced by overbreathing causes some degree of net vasodilation. The hypotension associated with hyperventilation appears to result in these experiments from the drop in cardiac output and to a lesser degree the relatively less than normal compensatory increase in total peripheral resistance.

Inhibition of endotoxin-induced pulmonary vascocontriction in dogs by alpha-methyl dopa.

The demonstration in a previous study of the effectiveness of an antihistaminic drug in blocking some of the systemic but not the pulmonary vascular effects of endotoxin led to the study of the effect of an inhibitor of serotonin synthesis, alpha-methyl 3,4-dihydroxyphenylalanine (α-m dopa). One group of seven dogs was pretreated with a single dose of 250 mg, and a second group of six animals with three doses of 250 mg, each given at 10-min intervals. Results in these two groups were compared with those in six control animals. Purified E. coli endotoxin, 1 mg/kg, was administered intravenously in all 19 experiments. Intravenous administration of α-m dopa alone had no effect on measured physiologic parameters. Compared with the endotoxin response in control animals, pretreatment with either dose level appeared to have no effect on the magnitude or duration of systemic arterial hypotension, portal venous hypertension, or drop in cardiac output. However, pretreatment with 250-mg and 750-mg doses was associated with significant reduction and abolition, respectively, of pulmonary arterial hypertension. The results are consistent with the interpretation that the pulmonary vasoconstrictive response to endotoxin is mediated through the release of serotonin and that α-m dopa blocks this response by interfering with the synthesis of this intermediary.

High serum transaminase activity in heart disease. Circulatory failure and hepatic necrosis.

A survey of all patients with very high serum glutamic oxalacetic transaminase activity encountered during a 30-month period at The New York Hospital revealed 17 patients with cardiac disease who had 1 or more serum glutamic oxalacetic transaminase (SGOT) determinations exceeding 500 units. None had clinical evidence of primary liver or gallbladder disease. Eleven were admitted with acute myocardial infarction, 6 with severe heart failure. All 17 developed hypotension or shock and all but 1 right heart failure prior to high SGOT activity. Several patients had abnormalities of liver function when SGOT activity was very high. In 4 there was an excessive increase in prothrombin time following administration of anticoagulants. In the 8 patients who came to autopsy there was histologic evidence of acute hepatic central necrosis. In 4 there was necrosis of both heart and liver, in 4 necrosis of liver alone. Clinical and autopsy data from a control series of patients with heart disease selected without regard for the level of SGOT activity corroborate the association between hypotension, central necrosis of the liver, and increased SGOT activity. Increase in venous pressure in the absence of hypotension was not associated with acute central necrosis or elevated SGOT activity. It is concluded that very high SGOT activity (&gt;500 units) in patients with heart disease is at least in part caused by acute hepatic central necrosis secondary to a drop in cardiac output and reduced hepatic blood flow. Caution is urged in the interpretation of increased blood activity of intracellular enzyme systems as evidence for myocardial necrosis. Acute circulatory changes may result in hepatic necrosis and increased blood enzyme activity without myocardial infarction.

Cardiac output during labor

1.1. In a study of 47 patients by a modified pulse pressure method, changes in cardiac output were recorded during late pregnancy, in labor, and in the early puerperium. This is the first report on cardiac output in labor.2.2. During effective contractions in labor, the cardiac output rises an average of 30.9 per cent over the output in the resting state.3.3. The act of bearing down in the absence of a contraction results in most cases in a small but transient drop in cardiac output. Bearing down with a contraction, however, may result in an actual increase in output.4.4. Pain and anxiety can produce significant elevations in cardiac output.5.5. Placental separation per se was not demonstrated to result in consistent variations in cardiac output. Contraction of the uterus post partum, however, may raise the output level significantly.6.6. Cardiac output appears to rise during the first stage of labor, and may rise even further at delivery. In some cases a small additional rise is seen in the first few minutes post partum. The output persists at a moderately elevated level for a variable period thereafter.

POSTURAL CHANGES IN CARDIAC OUTPUT AND RESPIRATION IN MAN

1. The acetylene method for the determination of cardiac output is considered in its practical details:(a) Modifications are recommended in the technique of sampling which reduce the possibility of vitiation of the results by the recirculation of acetylene‐containing blood.(b) The use of the usual modified Haldane apparatus for the gas analyses is open to serious error due to solution of acetylene in the CO2 absorbent. This analytical error can be eliminated by the use of a Van Slyke manometric apparatus.2. Studies in normal subjects of the postural changes in the circulation reveal an invariable increase of the arterio‐venous oxygen difference in the erect as compared with the reclining position: this is usually associated with a definite drop in cardiac output in the erect position, although this change may be masked by the increased rate of oxygen consumption usually found in the standing position.3. When a subject at rest on a tilting table is suddenly changed from the erect to the flat position, there occurs at once an increase in cardiac output as shown by an increase in the rate of oxygen uptake during the first 30 seconds or so after the change over. The increase in cardiac output calculated in this manner agrees closely with that calculated by the acetylene method.4. The pulmonary ventilation per 100 c.c. oxygen consumed is greater in the erect than in the reclining position. This hyperventilation can be correlated with the fall in absolute cardiac output which occurs in the erect position.This work was carried out with the aid of a grant for expenses from the Medical Research Council.