Low Cardiac Output State Research Articles

Effects of dopamine on haemodynamics and myocardial energetics in man: comparison with effects of isoprenaline and l-noradrenaline

The effects of dopamine (DOPA) on haemodynamics, coronary blood flow and myocardial oxygen requirements were compared with those of L-noradrenaline and isoprenaline (isoproterenol) in patients after open-heart surgery, performed because of mitral valvular and congenital heart disease. The patients were in low cardiac output state but not in shock. DOPA increased heart rate less than isoprenaline, averaging 22 and 31 beats/min, and was less arrhythmogenic. DOPA increased mean arterial pressure by an average of 7 mmHg, whereas isoprenaline had little effect; noradrenaline uniformly increased all measurements of arterial pressure. DOPA and isoprenaline increased cardiac index by an average of 1.01 and 0.94 1 min--1 m--2; noradrenaline did not significantly improve peripheral perfusion. DOPA and isoprenaline decreased systemic vascular resistance by an average of 465 and 549 dynes s cm--5; noradrenaline increased resistance in all patients. For similar cardiac outputs average urine flow increased more with DOPA (75 ml/h) than with isoprenaline (28 ml/h). DOPA increased coronary blood flow and myocardial O2 consumption by an average of 28 and 3.60 ml min--1 100 g--1, noradrenaline by 16 and 1.93 and isoprenaline by 62 and 4.25 ml min--1 100 g--1 respectively. Arterial--coronary sinus O2 differences remained unchanged (normal) with DOPA and noradrenaline and decreased with isoprenaline on average by 1.10 ml/100 ml. Myocardial lactate utilization was normal before and during catecholamine administration. It is concluded that, in its haemodynamic effects, DOPA is intermediate between noradrenaline and isoprenaline. The effects of DOPA on coronary blood flow and myocardial O2 consumption are closer to those of noradrenaline than of isoprenaline. DOPA increase coronary blood flow according to myocardial metabolic demand; it is not a potent primary coronary vasodilator. DOPA, although increasing myocardial O2 consumption more than noradrenaline, is by far less O2-demanding than isoprenaline. DOPA appears to be the superior vasoactive agent among the three catecholamines for the treatment of low cardiac output state in patients with preserved coronary reserve.

Anaphylactic Shock in the Monkey: its Hemodynamics and Mediators1

Anaphylactic shock (AS) was induced in 15 monkeys, and their hemodynamics were studied in order to identify the mechanisms initiating the low cardiac output (CO) state. Further, in 16 monkeys various substances were used with the aim of mimicking or antagonizing the changes in AS. Initial peripheral collapse was indicated by lowering of the right atrial pressure (RAP). The subsequent development of pulmonary hypertension increased RAP and, by extending venous pooling, reduced filling of the left heart. The degree of pulmonary hypertension or arterial hypotension was a poor indicator of the fall in CO. Hypoxemia and dysrythmias occurred occasionally, but early hemoconcentration was not found. Light depression of CO (—42%), due to venous pooling and reduction in left heart filling, could be corrected by fluid administration. In contrast, severe depression of CO (—81%) associated with ST‐T depression and with decreased cardiac contractility responded less to the fluid load, suggesting that myocardial failure was partly responsible for the low output state.Inhibition of prostaglandin (PG) synthesis by indomethacin did not prevent the development of AS. Injections of PGE2 and PGF2α, alone or together with histamine (Hi), did not mimic AS. PGE2 induced hypotension accompanied by an increase in CO, and PGF2α induced general vasoconstriction and a somewhat diminished CO. Hi induced hypotension and pulmonary hypertension; CO increased after low doses but decreased after sublethal doses. Compound 48/80, a liberator of Hi and slow‐reacting substance (SRS), imitated Hi effects initially, but later mimicked a minor state of AS. Infusion of FPL 55712, a selective antagonist of SRS, prevented AS, and general vasoconstriction occurred instead. In this model of AS, SRS is a more important mediator than Hi or PG.

Hemodynamic responses to dopamine infusion at controlled normal and low cardiac output states in the anesthetized dog

In order to isolate the renal and pulmonary vascular effects of dopamine, we employed a dog preparation utilizing fixed venous return in order to control cardiac output at either a normal or low flow state. Dopamine infusion was carried out at doses of 8 and 16 microng/Kg./min. Heart rate, mean systemic arterial pressure, mean pulmonary artery pressure, and renal blood flow were measured. Changes in mean systemic arterial pressure, mean pulmonary artery pressure, and renal blood flow were not significant at either doses of dopamine. There was a dose-related increase in heart rate, most significant with a dose of 16 microng/Kg./min. and low cardiac output. No evidence was found to substantiate the existence of a specific dopaminergic receptor in the renal vasculature when cardiac output was controlled.

Pharmacology of the renal circulation

The circulatory response of the kidney to drugs is conditioned by a variety of factors, such as basal vascular tone, dietary sodium and structural changes in the renal vasculature which accompany aging and disease. In addition, any drug which affects systemic arterial pressure will activate renal autoregulatory processes, which are superimposed upon the direct effects of the drug on the renal circulation. Renal autoregulation in addition to passive pressure effects probably accounts for the relative constancy of renal blood flow during the administration of renal vasodilators such as nitroprusside, diazoxide and minoxidil. Renal vasodilators which have minor effects on systemic arterial pressure, such as dopamine and glucagon, increase renal blood flow. These effects have been employed clinically in low cardiac output states. A variety of drugs affect the renal circulation by modifying the effects of endogenous vasoactive substances. The mechanisms of action include: receptor blockade; ex, adrenergic and Ag II-mediated vasoconstriction: enhanced production by the administration of biochemical precursors; ex, arachidonic acid and I-dopa: inhibition of endogenous production; ex, prostaglandin synthetase inhibitors: and inhibition of breakdown of endogenous substances; ex, converting enzyme inhibition. The effect of each of these interventions will depend in part upon the rate of endogenous production of the relevant vasoactive material. The administration of diuretics affects renal blood flow in individually distinctive ways, the mechanisms of which have been only partially elucidated.

Control of myocardial performance early after open-heart operations by vasodilator treatment

The hemodynamic effects of vasodilator treatment (afterload reduction) with nitroprusside at a constant heart rate were studied in 24 patients early after aorta-coronary bypass grafting. In 12 patients, dose-response relationships were determined. Graded incremental infusions of nitroprusside produced progressive decreases in mean arterial pressure (MAP), right and left atrial pressures, and stroke work index. Stroke volume index and cardiac index rose significantly until MAP was reduced below the range of 80 to 90 mm. Hg, and then they fell to base-line levels owing to insufficient preload. In an additional 12 patients, MAP was reduced with nitroprusside to the range of 80 to 90 mm. Hg, and left atrial pressure was then restored to base-line levels during continued vasodilator administration. This sequence resulted in further augmentation of stroke volume index to a level higher than that produced by nitroprusside alone. We conclude from this investigation that nitroprusside is a clinically useful agent for primary or adjunctive therapy of mild-to-moderate low cardiac output states immediate postoperatively and that simultaneous regulation of left ventricular preload and after load during its administration is necessary in order to achieve maximal hemodynamic benefit.

Echocardiographic and Phonocardiographic Confirmation of Suspected Caged Mitral Valve Malfunction

Seven patients studied by echocardiography with and without simultaneous phonocardiography for suspected malfunction of a caged mitral valve prosthesis are presented. In case 1, with inaudible prosthetic clicks, thrombosis of the cage and immobility of the ball were suggested by echocardiographic studies and confirmed at surgery. In case 2, simultaneous echocardiographic and phonocardiographic studies demonstrated wide and variable intervals between the aortic second sound the the opening click and also "sticking" of the ball. In case 3 a thrombus prevented full motion of the ball to the apex of the cage, which was seen on the echocardiogram, while in case 4, with a thrombus within the ventricle and prosthesis, the prosthetic opening click was present intermittently and was associated with only subtle echocardiographic changes. In case 5, echocardiographic studies demonstrated abnormal rocking of the cage secondary to severe prosthetic dehiscence. In case 6, dul prosthetic clicks were to be secondary to a low cardiac-output state. In case 7, with multiple valve prostheses, simultaneous echocardiographic and phonocardiographic studies allowed identification of individual valve sounds and abnormal timing of valve opening. Based on these studies, we believe that echocardiography and simultaneous phonocardiography can yield very useful information in the evaluation of patients with suspected malfunction of a caged mitral valve prosthesis.

Transposition of great arteries. Early results of Mustard's operation in paediatric patients.

Between May 1969 and June 1975, 43 patients with d-transposition of the great arteries, ranging in age from 2 months to 13 years (mean 19 months), underwent surgical correction. In the first 3 patients Mustard's original method was followed. Later a modified procedure was performed using a Teflon patch. Forty-two of the 43 patients had previously had 50 various palliative procedures, of which 30 were balloon atrial septostomy only. Five patients died in hospital (up to 5 weeks after operation). Of the 32 patients with simple repair of transposition of the great arteries (including 3 with ligation of a persistent ductus arteriosus), 3 died. One patient died as a result of complete AV block, one as a result of renal damage associated with unrelieved coarctation of the aorta, and one of cerebral infarction and peritonitis which probably were initiated preoperatively. Six patients who had additional surgery for pulmonary stenosis survived, including 3 patients who had closure of ventricur septal defect, including 2 who had debanding of the pulmonary artery, 2 died in a low cardiac output state. One infant operated on for subpulmonary stenosis developed permanent complete AV block and was successfully treated with a pacemaker. All the patients with combined operations had some problems postoperatively. The survivors improved greatly, but 2 patients died suddenly one, and one and a half years after the operation respectively.

Fatty acid and prostaglandin composition of left ventricular myocardium from dexamethasone-treated dogs with severe low output syndrome (LOS)

The effects of dexamethasone (DEX) administration on the left ventricular myocardial content of fatty acids and prostaglandins E 1, E 2 and F 2α were studied. Following a complete right and left cardiac catheterization, either DEX (8 mg/kg) or an equivalent volume of its vehicle was given intravenously 30 minutes prior to low output syndrome (LOS induction, and supplemental doses of DEX (4 mg/kg) or vehicle administered at 15 and 75 minutes post-LOS induction. Low output syndrome was induced by intravenous administration of a myocardial depressor protein (MDP) which has been isolated from the venom of the Western diamondback rattlesnake, Crotalus atrox . Neither DEX nor its vehicle had a significant effect during the entire experiment, that is, in the normal or low cardiac output state in most of the hemodynamic parameters investigated. The three hour mortality rate for the DEX-treated animals was 22% (n=10) while that of the control group was 41% (n=26) indicating that the beneficial effects of this corticosteroid are not really apparent from hemodynamic evaluation alone. Since DEX only had a significant post-LOS induction effect in maintaining a lower left ventricular end-diastolic and pulmonary capillary wedge pressures, a higher arterio-venous oxygen saturation difference, and a more efficient contractile state of myocardial fibers (V max), an indirect correlation to coronary arterial blood flow at the subcellular level was sought. To this effect, prostaglandins and specific lipid classes of left ventricular myocardium (LVM) from control and LOS animals receiving either vehicle or DEX were analyzed. Low output state induction alone raised myocardial PG levels above those of sham-catheterized animals; on the other hand, dexamethasone induced a significant decrease in the three prostaglandins studied when administered to control (no LOS) animals. In the presence of LOS, however, dexamethasone overrode in part the increase in PGE 1 and PGE 2 brought about by LOS while in the case of PGE 2α the LOS effect was totally prevented and its concentration was not significantly higher than in control animals receiving dexamethasone. LOS induction led to an increase in myristic and arachidonic acids and a decrease in palmitic and linolenic acids. Dexamethasone administration to control animals increased the concentration of stearic acid above all the other groups but decreased the concentration of linolenic acid when compared to DEX-treated animals with LOS or sham-catheterized animals. There were no significant differences in the total myocardial lipid among the four groups of animals studied. It is suggested that the potentially beneficial effects of corticosteroid administration to animals with low output syndrome are related to their effects on fatty acid and prostaglandin content of myocardium.

External Counterpulsation in Low Cardiac Output States

External counterpulsation represents a rational extension of the basic principles of counterpulsation as developed over the past 20 years. Its unique properties of being totally noninvasive, free of significant morbidity, and easily and quickly instituted clinically suggest that it may have a significant therapeutic role in the prevention and treatment of cardiogenic shock following acute myocardial infarction as well as being helpful in other cardiac disorders. Continuing evaluation is necessary, and it should be thought of as one of several useful mechanical circulatory assist devices now available to the internist, cardiologist, and surgeon caring for the critically ill patient.

Blood flow of the superior and inferior venae cavae in cardiogenic shock: a study with an emphasis of the role of the stretch receptors in the low pressure system.

Blood flow of the superior (SVC) and inferior venae cavae (IVC) was simultaneously and separately measured with two cannulating type electromagnetic blood flow probes inserted into the SVC and IVC of thirty two dogs during hypotensive and low cardiac output states in hemorrhagic shock and cardiogenic shock. Blood flow ratio of teh IVC to total venous return was expressed by IVCF/CO (per cent). It was 66.3 per cent in normal condition, but was decreased to 54.3 per cent in hemorrhagic shock. In four cardiogenic shock models, however, IVCF/CO changes little from the control to the initial phase of shock state. At least in part, the marked decrease of venous return from the IVC region in hemorrhagic shock was considered due to the increase of sympathetic nerve activity in that region mediated by baro-receptors in the high pressure system. The unchanged blood flow ratio of the SVC and IVC in cardiogenic shock was assumed that the high atrial or high ventricular endodiastolic pressure was an inhibitory factor of the sympathetic nerve activity by activating the stretch receptors existing the low pressure system including left ventricle. This hypothesis was proved by the experiments in which the renal vascular resistance was suppressed by stretch of the left atrium by either extraatrial mechanical traction or intraatrial balloon inflation in hemorrhagic shock or intracardiac decompression during cardiopulmonary by pass.

Dopamine in the treatment of low cardiac output state. Comparison with isoproterenol and L-NOREPINEPHRINE

Dopamine in the treatment of low cardiac output state. Comparison with isoproterenol and L-NOREPINEPHRINE

Residual or Delayed Lesions from Penetrating Cardiac Wounds

During an eight-year period, 76 patients with penetrating wounds of the heart were treated at our institution. Among the 56 patients who survived, there were 16 instances of delayed sequelae in 14 patients, an incidence of 25 percent. Residual sequelae from penetrating cardiac wounds may not be initially evident or detected because of the urgency when tamponade or bleeding are present or because of the low cardiac output state that may exist. For this reason and because delayed sequelae such as cardiac aneurysm may occur, close observation and repeat examination is required in patients who have sustained penetrating wounds. Because of the great variability of the hemodynamic significance of the intracardiac lesions and the similarity of the clinical signs between some of mem, cardiac catheterization and angiocardiography should be performed, if at all possible, in order to define the type lesions and their hemodynamic significance before they are repaired.

Letter: Intestinal ischemia and digitalis.

To the Editor. — In his letter (227:1263, 1974), Dr. Ko succinctly analyzed the dilemma of the elderly patient in whom mesenteric ischemia developed secondary to congestive heart failure. While it is probably true that digitalis preparations can intensify mesenteric vasoconstriction in these patients, it is equally clear that the continued decrease in cardiac output is also detrimental. In addition to the adrenergic mechanism suggested by Ko, it has been appreciated recently that in low cardiac output states the renin-angiotensin system is stimulated, 1 and the elevated level of circulating angiotensin II may well contribute to the mesenteric vaso constriction seen with low cardiac output. The specific agents that block the action of the renin-angiotensin system (eg, the Bothrops nonapeptide that inhibits the enzymatic conversion of angiotensin I to II and 1-sar, 8-ala, angiotensin that competitively inhibits angiotensin II) are available at present for experimental use. 1 In our laboratory,

Recovery From Acute Intestinal Ischemia Without Bowel Resection

Although intestinal infarction is often the result of a sudden massive occlusion of the superior mesenteric artery or vein, it also sometimes is caused by nonocclusive vascular insufficiency of the intestine secondary to a low cardiac output state. Such patients should be managed by vigorously treating the cause of the low cardiac output rather than undertaking resection of the bowel, which is seldom successful because the circulation is insufficient to permit primary healing.

The use of isoprenaline and alpha-adrenergic blockade in open heart surgery

One of the most important complications of open heart surgery is systemic arterial hypotension resulting from inadequate cardiac action. In most cases, this is the result of left ventricular pumping failure. The low cardiac index is accompanied by reflex circulatory adaptations mediated through the sympathetic adrenergic alpha receptors in the peripheral blood vessels. Vasoconstriction occurs to maintain cerebral and coronary blood flow with a rise in the central aortic pressure. The rise in peripheral vascular resistance has deleterious effects on the heart after intra-cardiac surgery, since there is a redistribution of blood towards the heart and an increase in the pressure work component of cardiac work. A vicious circle situation ensues with aggravation of left ventricular pumping failure and further reflex vasoconstriction. Analysis of the results of augmentation of cardiac output by the use of the beta-adrenergic-stimulating drug, isoprenaline, and the reversal of the potentially lethal rise in systemic vascular resistance by alpha-adrenergic blockade, has been made over the last 5 years. Prophylactic therapy with these drugs has led to a fall in the incidence of severe low cardiac output states occurring in the post-operative phase. The use of a specific competitive alpha-adrenergic-blocking drug, thymoxamine, to combat any potentially injurious rise in vascular resistance during cardiopulmonary by-pass allows for a low pressure work component of left ventricular function when the by-pass is terminated and, together with adequate blood volume and electrolyte replacement, an adequate cardiac index.

Intravenous dopamine in the treatment of myocardial dysfunction after open-heart surgery

Intravenous dopamine (6 to 33 μg per kilogram per minute) was administered to 15 consecutive patients developing hypotension after corrective valve surgery or saphenous vein bypass grafts. All were unresponsive to one or more of the usual inotropic agents (norepinephrine, metaraminol, isoproterenol, epinephrine, and glucagon). Ten of the 15 patients had adequate blood pressure restoration, increase in urine flow, and decrease in peripheral vasoconstriction. Of the 9 who no longer required dopamine for cardiovascular support, 6 were discharged from the hospital and remain well, 2 died of cerebral complications, and one of hyperkalemic cardiac arrest. One patient initially responded, but died during drug therapy. Five patients, unresponsive to dopamine as well as other pharmacologic agents, died. Dopamine was used continuously for over 60 hours in 5 patients and in concentrations greater than 20 μg per kilogram per minute in 8 patients. The data indicate that dopamine is a useful catecholamine in the treatment of patients with low cardiac output states after open-heart surgery.

Insulin secretion after open-heart surgery with particular respect to pathogenesis of low cardiac output state.

Insulin secretion after open-heart surgery with particular respect to pathogenesis of low cardiac output state.

Clinical evaluation of glucagon by continuous infusion in the treatment of low cardiac output states

A continuous infusion of glucagon in an average dose of 4 mg. per hour over several days produced distinct improvement in the clinical state of 12 of 16 patients. Improvement was noted by an increase in blood pressure and urinary output and decrease in dyspnea, pulmonary râles, diaphoresis, and peripheral edema when present. Serum potassium must be carefully monitored. The rise in blood glucose has not been a clinical problem. No cardiac arrhythmias were induced by glucagon, and as cardiac function improved, the heart rate usually decreased. Nausea was the most frequent side effect, but no toxic effects or tachyphylaxis were observed. Long-term therapy with glucagon infusion is both safe and highly efficacious in selected patients with severe cardiovascular disease states and is the treatment of choice in cardiac decompensation secondary to beta-blocking agents.

Observations on the regulation of cerebral blood flow in complete heart block.

The simultaneous effects of right ventricular pacing on cerebral blood flow (CBF) and cardiac function in complete heart block have not been reported. Catheters in the jugular bulb, right ventricle, and pulmonary and brachial arteries of five patients, aged 49 to 78 years, allowed studies at initial rates of 30 to 40 and during the tenth minute of pacing at 60, 70, 90, and 100 per minute. Mean initial cardiac output (CO) was 2.8 L per minute and increased 29% to 3.6 at a rate of 60 per minute ( P <0.01). Simultaneous mean control CBF was also low, but rose to 118% of control with pacing ( P <0.05). Systemic, cerebral, and pulmonary vascular resistances declined with these increases in flow as the elevated mean venous and arterial pressures remained stable. Mean arterial oxygen and carbon dioxide tensions and pH were normal at all rates. The parameters measured were not materially altered by pacing at rates above 60 per minute. The changes in CBF were well correlated with those of CO (r=0.81, P <0.01) and unrelated to simultaneous mean arterial or cerebral perfusion pressures. The alterations in CO were also unrelated to these pressures. The data clearly demonstrate a disturbance in CBF autoregulation, which may be a function of the low CO state.

Cardiovascular alterations during declining and steady-state low cardiac output secondary to coronary insufficiency in the dog

Summary A preparation in dogs is described in which the cardiac output was decreased in a stepwise manner and then maintained at a steady-state low value of approximately 50 per cent of the control value. This was accomplished by gradual, controlled constriction of the left circumflex coronary artery at its origin followed by serial interruption of left circumflex-anterior descending arterioarterial communications. The mean data collection period was 150 minutes. Cardiac output declined 51 per cent by 90 minutes. The mean steady-state low cardiac output period was 60 minutes. Aortic pressure declined 31 per cent by 90 minutes, but then increased to 16 per cent below control. Systemic resistance progressively increased. Left atrial pressure increased considerably, but gradually declined terminally. Peripheral arteriovenous per cent oxygen difference increased but was variable during the steady-state low cardiac output period. Cardiac rate diminished. Electrocardiographic changes of severe injury always occurred. The technique proved to be reliable and consistent for producing a low cardiac output state. In addition to permitting the biochemical and physiologic study of cardiogenic circulatory failure, this preparation could provide a much needed laboratory model for evaluating methods of cardiovascular assistance. The authors would like to thank Drs. J. Michael Criley, Bruce G. Brown, William R. Milnor, and Michael O'Rourke for review of the manuscript and to F. Wilbur Barnett, III, for technical help.