Biomedical subjects

P Kish

Publications and source records attributed to P Kish.

4 recordsLinked to original sources

PubMed1998

Effect of dietary vitamin A or N-acetylcysteine on ethylnitrosourea-induced rat gliomas.

It is our hypothesis that low grade gliomas are the glial counterparts of other precancerous lesions such as colon polyps and, therefore, suitable targets for chemoprevention. Steps in the molecular progression of gliomas have been described, indicating that an accumulation of abnormalities is required for progression to a high grade and interruption of this progression might be possible. An animal model of chemical glial carcinogenesis was used to test this hypothesis. Pregnant rats were injected intravenously with ENU (ethylnitrosourea) on the 18th day of gestation to induce gliomas in the offspring, which were randomized to receive control diet, diet supplemented with vitamin A palmitate, or diet supplemented with N-acetylcysteine. Animals exposed to ENU and receiving a control diet developed brain tumors and had a shortened life expectancy compared with rats unexposed to ENU. The animals treated with NAC showed no statistically significant delay in the time to tumor and no change in the histologic grade of the tumors when compared with animals receiving control diet, but the time to death from any cause of NAC treated animals differed significantly from untreated animals. Animals receiving high dose VA had statistically significantly prolonged time to tumor, survived significantly longer than untreated animals, but had no reduction in the total number of tumors or change in the histologic grade of their tumors. The theoretical basis of these results is likely due to the putative mechanism of action of these agents. These data indicate that glioma chemoprevention is possible and deserves further exploration.

Acetylcysteine↗

PubMed1986

Left ventricular function during lethal and sublethal endotoxemia in swine.

Our previous studies suggested that after a median lethal dose (LD50) of endotoxin, cardiac contractility was depressed in nonsurviving dogs. The canine cardiovascular system is unlike humans in that dogs have a hepatic vein sphincter that is susceptible to adrenergic stimulation capable of raising hepatic and splanchnic venous pressures. We retested the hypothesis that lethality after endotoxin administration is associated with cardiac contractile depression in pigs, because the hepatic circulation in this species is similar to that of humans. We compared cardiac mechanical function of pigs administered a high dose (250 micrograms/kg) or a low dose (100 micrograms/kg) endotoxin by use of the slope of the end-systolic pressure-diameter relationship (ESPDR) as well as other measurements of cardiac performance. In all the pigs administered a high dose, ESPDR demonstrated a marked, time-dependent depression, whereas we observed no significant ESPDR changes after low endotoxin doses. The other cardiodynamic variables were uninterpretable, due to the significant changes in heart rate, end-diastolic diameter (preload), and aortic diastolic pressure (afterload). Plasma myocardial depressant factor activity accumulated in all endotoxin-administered animals, tending to be greater in the high-dose group. In this group, both subendocardial blood flow and global function were depressed, whereas pigs administered the low dose of endotoxin demonstrated slight, but nonsignificant, increases in flow and function. These observations indicate that myocardial contractile depression is associated with a lethal outcome to high doses of endotoxin. One possible mechanism for this loss of contractile function may be a relative hypoperfusion of the subendocardium.

Animals↗

PubMed1985

Canine left ventricular function during experimental pancreatitis.

Left ventricular contractility following induction of experimental pancreatitis (EP) was studied. Contractility was evaluated by analyzing the left ventricular end systolic pressure-diameter relationship (sigma ES). Sigma ES is independent of large changes in preload, afterload, and heart rate, but sensitive to changes in ventricular contractility. Following injection of 100,000 IU trypsin in 4% taurocholate into the pancreas to induce EP, seven of eight dogs survived 5 hr. These dogs exhibited an initial significant reduction in mean arterial pressure (MABP) which stabilized at 90% of control at 3-5 hr post-EP. Cardiac output (CO) dropped slowly after EP induction (from 3.08 +/- 0.43 to 2.22 +/- 0.22 liters/min) associated with no significant change in peripheral resistance. Stroke work and stroke volume were markedly depressed reflecting the changes in MABP and CO. No consistent changes in +dP/dt or -dP/dt were observed. The ratio of endo/epicardial blood flow was unchanged as was blood Ca2+ levels throughout the experiment. Ventricular contractility as reflected by sigma ES tended to improve (from 49.7 to 69.6 mm Hg/mm at 4 hr following EP). Therefore, it was concluded that these animals exhibited no loss of ventricular contractility during EP.

Acute Disease↗

PubMed1984

Depression of left ventricular performance during canine splanchnic artery occlusion shock.

We studied canine left ventricular contractile performance following splanchnic artery occlusion (SAO) shock. We evaluated contractile performance by analyzing the left ventricular end systolic pressure-diameter relationship (sigma ES) because we have previously shown that sigma ES is independent of large changes in preload, afterload, and heart rate but sensitive to changes in ventricular contractility. Following release from 2 hours of SAO, seven dogs survived, five expired immediately, and ten expired between 0.5 and 3.5 hours (termed nonsurvivors, [NS]). The NS dogs exhibited slight tachycardia, slight increase in total peripheral resistance, marked decreases in +dP/dt, cardiac output, arterial blood pressure, stroke volume, and stroke work. Ventricular performance (sigma ES) declined with time following SAO release in the nonsurviving dogs; in contrast, surviving animals exhibited an augmentation of sigma ES during SAO and following SAO release. Sham dogs exhibited no time-dependent changes in sigma ES. The dogs that expired immediately following SAO release exhibited a precipitous decline in sigma ES from 43.0 +/- 9.0 to 23.0 +/- 4.8 mm Hg/mm within minutes of SAO release. We analyzed these data by Cox multiple regression analysis to determine the major covariates of survivability. The analysis revealed that sigma ES at the midpoint in time between SAO release and death was best correlated with the survival function. These results suggest that cardiovascular collapse of SAO shock is associated with an early and sustained loss of ventricular contractility.

Animals↗