Papineni S. Rao

Pregnancy-induced hypertension: Development of a model in the pregnant primate (Papio anubis)

Experiments were performed on two groups of pregnant baboons. In the experimental group, the subrenal aortic blood flow was reduced by 58% of its original value at 100 days of gestational age. In the control group, the blood flow was measured but not restricted. In the experimental group fetal death occurred in three of 12 animals following the use of a single left-flank incision to approach both the renal artery and the abdominal aorta. In the control group, pregnancies in eight of nine animals went successfully to 165 days. In the experimental group the development of hypertension, a decrease in plasma renin activity, an increase in renal resistance, an increase in serum uric acid, and the development of glomerular changes consistent with those seen in human pregnancy-induced hypertension were noted. These studies demonstrate that pregnancy-induced hypertension can be produced experimentally in a pregnant baboon, and this model should prove useful in expediting studies on the pathophysiologic features and treatment of this condition.

Nitric Oxide (NO) and Interleukin-1β (IL-1β) in Follicular Fluid and Their Correlation With Fertilization and Embryo Cleavage

PROBLEM: Using an IVF model, the goal of the study was to investigate the relationship between follicular fluid (ff) NO and IL‐1β levels, as well as their correlation with fertilization of mature oocytes and embryo cleavage rates.u2028 METHOD OF STUDY: Follicular fluid was collected from 17 patients at the time of transvaginal oocyte retrieval following controlled ovarian stimulation. Oocytes harvested from these follicles were followed through fertilization and embryo cleavage. The NO metabolites nitrate/nitrite (NO3/NO2) were measured using the Griess reaction as an indirect assessment of NO activity. IL‐1β was measured using a high sensitivity ELISA system (Amersham, UK). The Students t‐test was utilized for unpaired data with the means considered significantly different when P≤0.05.u2028 RESULTS: Follicular fluid NO3/NO2 levels were significantly lower in follicles containing mature oocytes that fertilized (n=30; 9.7±1.0 μM), versus those that did not fertilize (n=23; 15.4±2.4 μM; P<0.05). Follicles that contained oocytes that fertilized and went on to divide beyond the 6 cell stage had significantly lower ff levels of NO3/NO2 (n=18; 7.5±0.9 μM), as compared to ff that contained oocytes that did not fertilize or failed to develop beyond the 5 cell stage (n=35; 14.6±1.7 μM; P<0.01). No correlation was found between ff NO3/NO2 levels (n=28; 13.8±2.0 μM) and ff IL‐1β levels (n=28; 0.5±0.08 pg/mL). An analysis of ff IL‐1β levels in relation to fertilization and embryo cleavage rates revealed no correlation.u2028 CONCLUSIONS: Lower ff NO3/NO2 levels at the time of oocyte retrieval are associated with adequate fertilization and embryo cleavage rates. In our IVF model, no correlation was found between ff IL‐1β levels and ff NO3/NO2, fertilization, or embryo cleavage rates.

Dose-dependent effects of prostaglandin D2 on hemodynamics, renal function, and blood gas analyses☆

Dose-response effects of prostaglandin D2 (0.125, 0.25, 0.5, and 0.75 micrograms/kg/min) infused intravenously in pentobarbital-anesthetized dogs were studied with particular reference to renal, pulmonary, and systemic effects. Another group receiving the vehicle alone served as controls. Prostaglandin D2 administration resulted in a significant dose-dependent increase in renal artery flow, urine output, creatinine clearance, plasma renin activity, sodium excretion, potassium excretion, and pulmonary artery pressure. A significant decrease occurred in renal resistance and arterial PO2. There were no appreciable changes in mean arterial pressure, heart rate, hematocrit, platelet count, arterial pH, and PCO2. In the vehicle control group, all other parameters remained relatively stable, except for some increase in the mean arterial pressure, plasma renin activity, and potassium excretion. The results of this study suggest that prostaglandin D2 administered intravenously at levels lower than those required to produce adverse pulmonary and systemic effects will improve the renal blood flow and function.

Endotoxic shock in the primate: Effects of aspirin and dipyridamole administration☆

A primate model was utilized to study the cardiovascular and coagulation effects of endotoxic shock. The therapeutic effectiveness of drugs such as aspirin and dipyridamole, which diminish platelet aggregation and adherence, were evaluated. From the data, it appears that the kidney is a target organ in endotoxic shock, at least when a bolus injection of endotoxin is administered. The precipitate falls in the renal artery flow (p less than 0.01) and platelet count (p less than 0.01), which occur 3 minutes after the intravenous injection of endotoxin, can be prevented in part by pretreatment with aspirin (40 mg/kg of body weight). The changes in the coagulation profile were of less magnitude, and the fibrin degradation products appeared late in the group pretreated with aspirin as compared to the other groups. The combination of dipyridamole and aspirin was not as effective as aspirin alone in achieving the apparently protective effect. The study suggests that the administration of aspirin to patients with gram-negative infections may be beneficial.

Septic shock (endotoxic shock).

n The pathophysiology, clinical aspects, medical, and surgical management of endotoxin shock are reviewed. In the primate, the pathophysiology of endotoxin shock is contributed to by selective vasopasm, disseminated intravascular coagulation, and reduced myocardial response to sympathetic stimuli. Studies in the baboon measured various parameters of hemodynamics and coagulation, catecholamines, and some biochemical changes following the injection of a single bolus of endotoxin. Hemodynamic studies pointed to the kidney as a primary target organ. Coagulation changes included alterations in factor XII and XIII (and others) and plasminogen. Deposition of fibrin was also noted. Neurohormonal studies using tritiated norepinephrine showed a sharp rise in catecholamines 3 minutes after injection of endotoxin followed by a return to normal within 120 minutes, confirming the role of vasopasm in reducing renal perfusion early in shock. Prevention of septic shock is the best way to eradicate the extremely high reported mortality rates; infected abortion, chorioamnionitis, and pyelonephritis should all be warning signals. Methods of monitoring the patient in septic shock with special attention to blood pressure, central venous pressure, blood volume changes, and urinary output are discussed. Early surgical intervention and the proper use of vasomotor drugs and corticosteroids enhance patient survival.n

The effect of prostaglandin D2 (PGD2) on circulating eosinophils

Infusion of prostaglandin D2 (PGD2) into dogs for 60 minutes at a rate of 1 microgram/kg/min produced a marked and rapid reduction in circulating eosinophils within 2 minutes, without any significant change in neutrophil count. Recovery was also rapid, with levels similar to those of a control group of dogs being reached 60 minutes after finishing the infusion. In dogs given PGD2 the hematocrit rose more rapidly than in the control group. The platelet count did not alter significantly.

Prostaglandin D2 in canine endotoxic shock: Hemodynamic, hematologic, biochemical, and blood gas analyses☆☆☆

This canine study was designed to evaluate the effects of the intravenous infusion of coliform endotoxin with a simultaneous infusion of prostaglandin D2 (PGD2) on hemodynamics, blood gas, blood chemistry, and some hematologic parameters. The information derived from the present study supports the view that the intravenous administration of PGD2 moderates the effects of endotoxin, with its main beneficial effect being on the renal vascular bed. Treatment with PGD2 did not change the endotoxin-induced hemoconcentration, or the reduction in the platelet and white blood cell counts. However, four of nine animals survived more than 7 days when treated with PGD2, whereas without it only one of nine animals survived the administration of the same dose of endotoxin. Although the mechanism of action is not clear, the correlation between PGD2 infusion and improved renal blood flow warrants further study in endotoxic shock.

Intravenous versus intraperitoneal administration of dextran in the rabbit: effects on fibrinolysis.

Adhesions are the leading cause of small bowel obstruction and a frequent cause of failure of infertility operations. Fibrinolysis is involved in the formation and resolution of adhesions. Although intravenous dextran (Macrodex) is known to augment intravascular fibrinolysis, the effects of intraperitoneal dextran (Hyskon) on fibrinolysis have not been extensively studied. A fibrin plate assay system was used to assess plasminogen activator activity of rabbit peritoneum and plasma after treatment with intraperitoneal or intravenous dextran 70. Hyskon significantly reduced the ability of severe trauma to depress plasminogen activator activity of visceral peritoneum and was capable of direct plasminogen activation. Untraumatized or minimally traumatized peritoneum was not affected, nor was plasminogen activator activity of plasma. Pulmonary effusions and perioperative deaths were significantly associated with the use of Hyskon.

Septic shock in obstetrics.

Septic shock in obstetric patients can be prevented by recognition of patients at risk and aggressive intervention in the warm-hypotensive phase. These patients must be monitored closely. Rarely will an obstetrical floor be capable of providing adequate monitoring of these patients; therefore, the patient should be transferred to an intensive care unit. Individualize therapy, but do not procrastinate in the surgical removal of the nidus of infection.

Endotoxic shock in the primate: some effects of dopamine administration.

The circulatory effects of dopamine (3,4-dihydroxyphenylethylamine) in baboons with endotoxic shock were studied. A beneficial effect was seen in all cardiovascular parameters studied. Cardiac output was better maintained, and this was primarily due to an increase in the stroke volume. The renal artery flow was improved with a decrease in the renal resistance in the dopamine-treated group when compared with the group receiving endotoxin alone. Arterial pH and PO2 did not show significant changes. A rise in blood lactic acid level and a decrease in arterial PCO2 were consistent findings whether or not the animals received dopamine. This study supports the view that dopamine improves the cardiovascular status of the subhuman primate in endotoxic shock and has implications with regard to the patient with endotoxic shock.