Adverse Hemodynamic Changes Research Articles

The Myocardial Contractile Responses to Protamine Sulfate and Heparin

The administration of protamine sulfate for the reversal of heparin anticoagulation has been associated with adverse hemodynamic changes including hypotension and decreased cardiac output. The possible direct toxic effect of protamine on human right atrial trabeculae contracting isometrically in vitro was studied. Muscles were stimulated to contract at 1 Hz in Tyrode's solution (maintained at 34°C, pH 7.4) into which protamine was continuously added. Following a polynomial regression analysis, a parabolic dose-response curve resulted. The equation was: y = 95.13 + 38.76x − 278.71x 2 where y = relative developed force and x = concentration of protamine (milligrams per milliliters) ( r = 0.82). The estimated concentration of protamine resulting in 50% developed force was 0.48 mg/ml. In a second series of experiments, protamine was added to the bath along with a neutralizing amount of heparin. This resulted in a limited reduction in the fall of relative developed force. Thus, protamine in high concentrations alone or in complex with heparin has a direct toxic effect on human myocardial muscle mechanics, and care is warranted in its clinical use.

… and high dose infusions produce no adverse haemodynamic changes in patients with coronary disease

… and high dose infusions produce no adverse haemodynamic changes in patients with coronary disease

Evaluation of potential adverse effects of sodium nitroprusside during pacing-induced myocardial ischaemia in man.

To elucidate the potential harmful effects of sodium nitroprusside (NP) on myocardial ischaemia, eleven patients with coronary artery disease were studied before and during two doses NP infusion. The infusion rates were adjusted to reduce systolic aortic pressure by 10-20 mmHg and to between 100 and 110 mmHg. Myocardial haemodynamic and metabolic measurements were undertaken in sinus rhythm and during pacing-induced angina pectoris. The procedure was repeated at the low and high dose NP using the same pacing rate. One patient did not develop ischaemia and was excluded. Low dose NP reduced ischaemia slightly, whereas the higher dose had no effect despite falling indices of cardiac work. The oxygen uptake was maintained except at high dose treatment during pacing due to an increased catecholamine stimulation. The transmural perfusion gradient was unchanged at low dose NP, but fell at the higher dose suggesting reduced perfusion of ischaemic tissue. High dose NP also decreased coronary arteriolar resistance considerably which may have induced a coronary 'steal' effect. Thus, NP may induce adverse haemodynamic and metabolic changes which counteract the beneficial actions of the drug on ischaemia when used in high doses and in patients without heart failure.

Depressed cardiovascular function and altered platelet kinetics following protamine sulfate reversal of heparin activity

This investigation documented the hemodynamic effects of rapid intravenous and intraarterial administration of protamine sulfate, altered platelet kinetics associated with intravenous protamine sulfate administration, and a possible method of reducing protamine sulfate-induced hypotension. Thirty-six anesthetized dogs underwent continuous hemodynamic monitoring prior to heparinization (150 U/kg) and for 30 minutes after rapid reversal with protamine sulfate (1.5 mg/kg over 10 seconds). Platelet counts, platelet aggregation, and serum thromboxane B2 levels were also assessed. Intra-arterial protamine sulfate administration caused fewer adverse hemodynamic changes than intravenous administration, including significantly (p < 0.05) reduced falls in mean arterial pressure (− 10 vs. − 35 mm Hg), cardiac output (−0.2 vs. −0.6 L/min), femoral artery blood flow (+34 vs. −16 ml/min), and superior mesenteric artery flow (+107 vs. −48 ml/min). Thrombocytopenia following protamine sulfate administration was the same in the two groups. Marked hypotension accompanying intravenous protamine sulfate administration was completely attenuated by a small dose of protamine sulfate (0.75 mg/kg) administered prior to heparinization. Similarly, the thrombocytopenia caused by intravenous administration was significantly lessened by protamine sulfate pretreatment (74% vs. 23% reduction; p < 0.01). These observations have important implications for both experimental and clinical use of heparin and protamine sulfate.

Role of reactive hyperreninemia in blood pressure changes induced by sodium depletion in patients with refractory hypertension.

Sixteen patients with refractory hypertension were submitted to vigorous sodium depletion while cardiovascular homeostasis was monitored with measurements of hormonal and hemodynamic parameters and repeat saralasin tests. This regimen resulted in a negative sodium balance by an average of 300 mEq. The loss of sodium closely correlated to the decrease of body weight (r = 0.70, p less than 0.005). Blood pressure (BP) decreased from 176/166 +/- 8/3 to 155/109 +/-6/3 mm Hg. There was a significant correlation between percent increments in plasma renin activity (PRA) and the rise in plasma norepinephrine (r = 0.68, p less than 0.05) and a close negative correlation between percent increase in PRA and the ratio of fall in mean blood pressure (MAP) per unit of weight loss (r = -0.73, p less than 0.005). Thus, patients with the least percent increase in PRA demonstrated the greatest fall in BP per unit of weight loss, indicating that relative rather than absolute elevation of renin may be the factor limiting antihypertensive efficacy of sodium depletion. Sodium depletion induced increase in peripheral resistance and decrease in cardiac output, both mostly attributable to relative hyperreninemia. Indeed, the adverse hemodynamic changes were reversed by angiotensin inhibition, during which BP normalized. It is concluded that vigorous sodium depletion complemented by angiotensin blockade or suppression with sympatholytic agents improves management of otherwise refractory hypertension.

Propranolol-induced hemodynamic changes and thermogenesis in the pigeon

1. Single dose of D,L-propranolol injected intravenously in unanaesthetized pigeons maintained at 22°C room temperature produced significant increase in venous hematocrit and pCO 2 values but lower pH and pO 2 values than in the saline-injected control group. 2. There was a post-injection fall in plasma sodium content which was identical in both the propranolol and saline groups, whereas potassium level tended to be higher in the former group. 3. Since there was no change in the size of erythrocytes and the plasma total protein content was relatively higher in the propranolol group than in the saline group, it was suggested that the higher hematocrit observed was due to a possible leakage of plasma fluid into the surrounding extracellular space. 4. On the other hand, intravenous administration of noradrenaline produced no change in hematocrit in spite of the severe acidosis caused. 5. These results tend to indicate that hypothermia produced by propranolol birds is most likely a result of adverse hemodynamic changes, rather than the blockage of any specific receptor mechanism involved in resistance to cold.

Adverse hemodynamic and ultrastructural changes in dog hearts subjected to protein-calorie malnutrition

In the absence of thiamine deficiency, the specific effects of protein-calorie malnutrition on left ventricular (L.V.) function are unknown. Mature beagle dogs of both sexes were subjected to a hypocaloric, nitrogen-poor diet which resulted in a weight loss of approximately 40 per cent after seven weeks. Following preparation of this nutritional model, myocardial contractility was assessed acutely by obtaining isovolumetric L.V. contractions on cardiopulmonary bypass at constant heart rate, mean aortic pressure, and at a wide range of end-diastolic volumes. These changes were compared to a matched group of animals which were normally fed. There were consistent decreases in L.V. compliance in malnourished animals compared with normals; indices of ventricular contractility per se (L.V. dp dt , force-velocity relations, peak developed L.V. pressure) were also diminished in the experimental animals. Myocardial concentration of glycogen was diminished in malnourished compared to control animals. Light and electron microscopic examination confirmed the presence of myofibrillar atrophy in the presence of interstitial edema. These results suggest that protein-calorie malnutrition seriously interferes with normal L.V. function in the experimental animal by reducing compliance as a result of “starvation edema,” and by reducing myocardial contractility associated with atrophy of the myofibers.