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Biomedical subjects

H B Hechtman

Publications and source records attributed to H B Hechtman.

At least 181 records · Page 10Linked to original sources

Maintenance of cardiodynamics with aspirin during abdominal aortic aneurysmectomy (AAA).

The importance of prostacyclin (PGI2) and thromboxane (Tx) medication of depressed cardiac performance during abdominal aortic aneurysm operative surgery was studied by contrasting the effects of 650 mg aspirin administered 12 hours before operation to that of a placebo. In 11 patients who received a placebo, the stable metabolite of PGI2, 6-keto-PGF1 alpha rose from 0.050 +/- 0.032 eta grams/ml to 0.419 +/- 0.257 eta grams/ml (p less than 0.01) 30 minutes after the skin incision. The stable metabolite of TxA2, TxB2 did not increase until the aorta was clamped when TxB2 rose from 0.089 +/- 0.054 eta grams/ml to 0.193 +/- 0.138 eta grams/ml (p less than 0.05); this was prior to blood transfusion. During aortic clamping cardiac output decreased 27% (p less than 0.001). In vitro testing of patient plasma showed: 1) depressed developed tension (Tpd) of a rat papillary muscle by 16% (p less than 0.05); 3) reduction of Ca++-ATPase and Mg++-ATPase activity in a rat myocardial subfraction of sarcoplasmic reticulum (p less than 0.05); 3) reduction of Ca++-ATPase in a rat myocardial subfraction of myofibrils (p less than 0.01). Aspirin administered to 11 patients produced no measurable changes in blood loss or fluid requirements. Aspirin lowered preoperative 6-keto-PGF1 alpha and TxB2 levels (p less than 0.01) and prevented an increase of either agent during operation. The low Tx levels were associated with a stable cardiac output during aortic clamping. Further, plasma obtained from aspirin-treated patients did not depress papillary muscle contractility nor decrease ATPase activity of either myocardial subfraction. The observation that TxB2 when added to a papillary muscle or myocardial subfractions, did not decrease Tpd or ATPase suggests that TxB2 plays an indirect role in altering cardiac muscle activity. The results indicate that Txs modulate cardiac depression, which can be prevented with 650 mg aspirin before operation.

6-Ketoprostaglandin F1 alpha↗

Cardiopulmonary function following transfusion of three red blood cell products in elective abdominal aortic aneurysmectomy.

In order to evaluate the importance of red cell O(2) affinity of transfused blood on cardiac performance and adverse effects of transfusion on lung function, a prospective double-blind protocol was used in 27 patients undergoing abdominal aortic aneurysmectomy. Three types of blood were administered: packed red cells (PC), washed red cells (WC) and high 2,3 DPG red cells (2,3 DPG). An average of 4.5 units of blood was used per patient. Transfusion of 2,3 DPG blood resulted in maintenance of in vivo P(50) during surgery and an increase to 31.2 torr after operation (p < 0.001). An intraoperative fall in in vivo P(50) to 23.2 +/- 2.0 torr was observed in patients who were transfused with PC (p < 0.001) and to 25.1 +/- 2.6 torr with WC (p < 0.005). A fall in body temperature averaging 2.2 C intraoperatively was noticed in all three groups. After operation, in vitro P(50) decreased in patients transfused with PC (p < 0.005) and WC (p < 0.005) while it remained unchanged in the high 2,3 DPG group. This was consistent with the decrease of red cell 2,3 DPG in the PC (p < 0.001) and WC groups (p < 0.01) and maintenance in the 2,3 DPG group. Left ventricular stroke work and volume loading Starling type myocardial performance curves were similar for the three groups. Microaggregates measured by Coulter counting and screen filtration pressure were the same for all three products in samples drawn on both sides of the 40 microm transfusion filter. There was no relationship of transfusion volumes or type of blood product to changes in lung function (physiologic shunting, dynamic compliance and pulmonary arterial pressure) in the three groups of patients. The false negative, beta, error of missing a true 25% difference was less than 10%. It is concluded that 2,3 DPG enriched red cells improved oxygen availability, but that a 4.5 unit transfusion of any of the three blood products did not influence lung function or myocardial performance following aneurysmectomy.

2,3-Diphosphoglycerate↗

Inhibition of thrombocytopenic petechiae by exogenous serotonin administration.

The effect of serotonin on vascular fragility, visible as petechiae, was examined in antiplatelet serum-induced thrombocytopenic hamsters. Serotonin was administered intravenously or intraperitoneally, and following a single injection of 0.5 mg/100 g body weight, a temporary inhibition of petechial formation for approximately 1 h was observed. Repeated serotonin injections maintained animals free of petechiae for the 4-hour period of administration. Plasma levels of serotonin and the effect of serotonin on cutaneous perfusion were not significant factors in the observed inhibition of petechiae. The data suggest that in normal animals platelet serotonin may contribute more to maintaining microvascular structural integrity than platelet adhesion.

Animals↗

Prostacyclin reversal of lethal endotoxemia in dogs.

Severe endotoxemia, a condition where microembolization and intravascular coagulation are thought to play important roles, was treated experimentally with prostacyclin (PGI(2)). In a study of 24 dogs, 8 control animals injected with 1.75 mg.kg(-1) of endotoxin died within 24 h. Six animals given intravenous aspirin 100 mg/kg, 30 min after endotoxin died. 9 of 10 dogs infused with 100 ng PGI(2).kg(-1).min(-1) for 3 h, given 30 min after the injection of endotoxin survived 24 h (P < 0.025). Injection of endotoxin resulted in a: (a) maximal 62% fall in mean arterial pressure (P < 0.001); (b) transient doubling of mean pulmonary arterial pressure (P < 0.001); (c) initial 70% drop in cardiac index (P < 0.001); (d) decline in blood platelets from 213,700 to 13,700/mm(3) (P < 0.001), and leukocytes from 7,719 to < 750/mm(3) (P < 0.001); (e) depressed urine output (P < 0.001); (f) 34% decrease in blood fibrinogen (P < 0.01) and an increase in fibrin degradation products > 50 mug/ml (P < 0.001); (g) fivefold increase in circulating cathepsin D titer (P < 0.005) and (h) increase in blood norepinephrine (P < 0.005), dopamine (P < 0.005), and epinephrine (P < 0.001). Aspirin treatment led to an increase in mean arterial pressure (P < 0.001) and mean pulmonary arterial pressure (P < 0.005), but cardiac index, urine flow, platelets, leukocytes, fibrin degradation products, and cathepsin D levels remained similar to untreated controls. After infusion of PGI(2) there was a: (a) prompt increase of cardiac index to base-line levels; (b) late increase in mean arterial pressure (P < 0.005) after the discontinuation of PGI(2) treatment (c) restoration of urine output; (d) increase in circulating platelets to levels still below base line but above untreated control animals (P < 0.05); (e) no effect on circulating leukocyte levels; (f) fall in fibrin degradation products to 11.2 mug/ml (P < 0.05); (g) decline in cathepsin D levels to values 60% lower than the untreated controls (P < 0.025); and (h) reduction in plasma norepinephrine levels to base line at 4 h (P < 0.005). Although the mode of PGI(2) action is not clear, it is effective in the treatment of experimental endotoxemia.

Animals↗

Preservation of platelets and their function in prolonged cardiopulmonary bypass using prostacyclin.

The effects of prostacyclin (PGI2) with and without heparin were studied in 28 dogs that underwent 2 hours of cardiopulmonary bypass. Five groups were created: group I (six dogs) received heparin, 1.25 mg/kg; group II (six dogs) received low-dose heparin, 0.5 mg/kg, and PGI2, 500 ng/kg/min; group III (six dogs) received low-dose heparin alone; group IV (four dogs) received PGI2, 500--1000 ng/kg/min; and group V (six dogs) received ibuprofen, 12.5 mg/kg, dipyridamole, 1 mg/kg, PGI2, 20 ng/kg/min, and low-dose heparin. Significant clot deposition occurred in the oxygenators in groups III, IV and V. Platelet counts decreased to a mean of 36.8 +/- 5.7% (+/- SEM) of control in group I, which had normal clinical heparin dose for dogs, but to only 74 +/- 7% of control in group II. This improvement was significant (p less than 0.005). Platelet aggregation induced by adenosine diphosphate 60 minutes after CPB showed poor aggregation in group I but almost normal aggregation in group II. Protamine was unnecessary in groups that received PGI2. PGI2 in combination with low-dose heparin provides adequate anticoagulation during cardiopulmonary bypass in dogs, preserves platelet number and function and is associated with minimal postoperative bleeding.

Animals↗

Serotonin uptake by isolated adipose capillary endothelium.

The uptake of serotinin (5-hydroxytryptamine, 5-HT) by endothelial cells was studied in freshly isolated capillary and other microvessel (< 50 micrometers, inner diameter) endothelium obtained from rat epididymal fat pads. Endothelial cells incubated with [3H]-5-HT removed 60 pmol of [3H]-5-HT per mg of protein at 1 hr, an apparent Km of 3 X 10(-7) M and a Vmax of 20 pmol/mg of protein, measured at 15 min, were obtained. Uptake of 5-HT (10(-6) of M) was inhibited by ouabain, selected metabolic inhibitors (iodoacetate, 2--4 dinitrophenol and sodium azide), 4 degrees C, tryptamine (10(-5) M and the 5-HT antagonists, fluoxetine and imipramine (10(-5) M and 10(-4) M, respectively). At concentrations of 5-HT greater than Km value, uptake appears to be principally by nonfacilitative diffusion rather than by carrier-mediated transport.

Adipose Tissue↗

Peritoneal lavage in blunt abdominal trauma.

A prospective study of an Intracath method of diagnostic peritoneal lavage was done of 100 patients with blunt abdominal trauma. Initial results in dogs confirmed the reliability and sensitivity of the technique. In patients, it proved to be 96 per cent accurate. Fifty-eight patients had true-positive results, and in 52 of these, subsequent laparotomy demonstrated significant hemoperitoneum and intra-abdominal injury. Six patients had intra-abdominal injuries of limited significance. Thirty-eight of these patients were considered to have true-negative results. In one patient, false-negative, signs of intra-abdominal bleeding later developed, and a splenectomy was performed without incidence. There were three false-positive results. These patients underwent laparotomy and recovered without a problem. The only complications noted were puncture of the urinary bladder in one patient and subcutaneous infusions of lavage fluid in two patients which were recognized during the procedure. Results of this study demonstrate the safety and reliability of the Intracath method of peritoneal lavage for patients with blunt abdominal trauma.

Abdominal Injuries↗

Volume loading and vasodilators in abdominal aortic aneurysmectomy.

Preoperative infusion of volume to increase the wedge pressure will maintain stable flow and arterial pressure at the time of aortic declamping. Usually 1,500 ml of balanced salt solution given with 75 g of albumin is sufficient to accomplish this purpose. Pressor or inotropic agents are not required. In our experience 14 percent of patients will have a down-slope in the preoperative myocardial performance curves. In these persons, volume infusions should be adjusted to keep the pulmonary arterial wedge pressure on the ascending portion of the curve. The use of vasodilator agents in normotensive patients has a deleterious effect on cardiac performance.

Aged↗

Improved oxygen delivery to the myocardium during hypothermia by perfusion with 2,3 DPG-enriched red blood cells.

The oxygen affinity of red cells increases stepwise with temperature reductions below 37 degrees C. In vitro studies demonstrated that biochemically modified red cells with increased 2,3 diphosphoglycerate (2,3 DPG) (150% and 250% of normal) exhibited significantly less oxygen affinity at 24 degrees C than did unmodified cells. At 15 degrees C, significant attenuation of affinity was observed with 250%, but not 150%, of normal 2,3 DPG cells. Measurements made of isolated fibrillating dog hearts during perfusion at 24 degrees C alternately with unmodified (80% of normal 2,3 DPG) and modified (300% of normal 2,3 DPG) red cells demonstrated significantly greater oxygen consumption, higher coronary sinus partial pressures of oxygen and carbon dioxide, higher in vitro P50 values, and lower arterial and coronary sinus lactate levels during perfusion with modified as compared with unmodified cells. This evidence, indicating improved oxygen delivery to hypothermic dog hearts by red cells with 300% of normal 2,3 DPG activity, suggests that high 2,3 DPG cells might protect myocardial tissue in patients undergoing hypothermic cardiac operation.

Animals↗