Biomedical subjects

G P Toorop

Publications and source records attributed to G P Toorop.

10 recordsLinked to original sources

PubMed1998

Focal cerebral ischemia in the mouse: hypothermia and rapid screening of drugs.

1. We have investigated the ability of several compounds to diminish both infarct area and volume induced by middle cerebral artery occlusion in the mouse. 2. Lifarizine, ipsapirone and N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl (DPPE) all reduced both infarct area and volume. Ifenprodil diminished the infarct area, but the effect on total infarct volume was much less pronounced. 3. In addition, we tested the protective effects of some other drugs on infarct area only. Nimodipine, verapamil, diltiazem, N-[1-[4-(4-fluorophenoxy)butyl]-4-piperidinyl]-N-methyl-2-benzothiazo lamine (R56865) and sabeluzole had no effect on infarct area. (S)-Emopamil significantly diminished infarct area. 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) also diminished infarct area significantly. 4. In some brain ischemia models hypothermia protects against ischemic damage. Mild hypothermia had no effect on infarct area in the present mouse model of focal ischemia.

Animals↗

PubMed1991

Systemic and regional hemodynamic effects of the 5-hydroxytryptamine1A receptor agonists flesinoxan and 8-hydroxy-2(di-N-propylamino)tetralin in the conscious rat.

The systemic and regional hemodynamic effects of the centrally acting 5-Hydroxytryptamine1A (5-HT1A) receptor agonist flesinoxan (0.5 and 2.5 mg kg-1, intraarterially, i.a.) were investigated in conscious freely moving spontaneously hypertensive rats (SHR) and compared with those of 8-hydroxy-2(di-N-propylamino)tetralin (8-OH-DPAT) (0.1 and 0.5 mg kg-1, i.a.). In one group of animals, cardiac output (CO) was measured with a precalibrated electromagnetic flow probe around the ascending aorta. In another group, regional vascular conductances were measured using radioactive microspheres. Flesinoxan and 8-OH-DPAT dose dependently decreased blood pressure (BP) (22 +/- 5 and 13 +/- 4%, respectively, at the highest dose) mainly resulting from an increase in total peripheral vascular conductance (TPC) (34 +/- 12 and 16 +/- 3%, respectively) since there was no effect on CO. Both drugs reduced heart rate (HR) (17 +/- 4 and 20 +/- 4% for flesinoxan and 8-OH-DPAT, respectively, at the highest dose). Flesinoxan and 8-OH-DPAT showed a qualitatively similar pattern with regard to their effects on vascular conductances, causing increases in vascular conductances in the heart and skeletal muscles in contrast to results in a saline-treated group. Vascular conductances in the lungs were markedly increased by both flesinoxan and 8-OH-DPAT, which may indicate that the conductance in the arteriovenous shunt vessels was enhanced. These results demonstrate that flesinoxan and 8-OH-DPAT elicit a qualitatively similar systemic and regional hemodynamic profile in conscious SHR. Furthermore, the increase in TPC appears to be due mainly to vasodilatation in the skeletal muscles.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1990

Geometry and pump function in cardiac ventricular hypertrophy.

Ventricular pump function can be quantified by the inverse relation between pressure and output, i.e., the pump function graph, which is obtained by varying arterial load without changing end-diastolic volume, inotropic state and heart rate. The ratio of pressure and output, i.e., the peripheral resistance, can be represented in the same graph by a line through the origin. The 2 pressure-output relations intersect in the working point, i.e., the pressure and flow at the prevailing steady state. In normal, anesthetized cats the ventricle appears to be matched to the arterial load in the sense that the working point is found at the optimal power, i.e., the optimal value of the product of pressure and output along the pump function graph. To maintain this matching criterion during pressure overload, the ventricular volume has to remain the same while thickening of the wall takes place: concentric hypertrophy. With volume overload, matching would be preserved with eccentric hypertrophy. Because volume and pressure overloads typically lead to eccentric and concentric hypertrophy, respectively, the matching criterion may be a valuable predictor of the geometric changes found with changes in load. This idea was further investigated experimentally by determining the position of the working point in the perinephritic cat that had 1 kidney removed and the other wrapped in cellophane for 15 to 26 weeks. The working point was no longer found at the optimal power, indicating that either matching was permanently comprised or that the ventricle was still trying to restore matching.

Animals↗

PubMed1990

Effects of nitroprusside on myocardial blood flow and oxygen consumption in conscious lambs with an aortopulmonary left-to-right shunt.

We studied the effect of vasodilation on regional myocardial blood flow and oxygen consumption of the left ventricular free wall by infusing 10 micrograms/kg/min sodium nitroprusside into 7-week-old conscious lambs with and without aortopulmonary left-to-right shunts. Resting myocardial oxygen consumption in the 13 shunt lambs was significantly higher than in the nine control lambs (989 +/- 104 [+/- SEM] vs. 432 +/- 41 mumol/min/100 g left ventricle). This was achieved by a significantly higher left ventricular myocardial blood flow (294 +/- 33 vs. 143 +/- 16 ml/min/100 g left ventricle) because the arteriovenous oxygen concentration difference across the left ventricular free wall was similar in shunt and control lambs. Infusion of nitroprusside did not significantly change myocardial oxygen consumption and regional myocardial blood flows at 10 and 50 minutes after the onset of the infusion. This occurred despite a substantial drop in aortic and left atrial pressures and stroke volume, which decreases wall stress as well as external work of the left ventricle. Heart rate, however, increased significantly. We postulate that, during infusion of nitroprusside, the potential decrease in myocardial oxygen consumption due to a decrease in wall stress and external work of the left ventricle is neutralized by the consequences of the increased heart rate. In view of this and because of its hemodynamic effects, we do not consider sodium nitroprusside useful in the treatment of circulatory congestion in patients with left-to-right shunts, normal arterial pressures, and normal systemic blood flows.

Anastomosis, Surgical↗

PubMed1989

Circulatory effects of sodium nitroprusside in the conscious lamb with an aortopulmonary left to right shunt.

We studied the effect on the circulation of reducing peripheral vascular resistance by infusing sodium nitroprusside into lambs of three different age groups (subgroup A, 11-26 days, subgroup B, 32-52 days, and subgroup C, 61-88 days of age) with and without an aortopulmonary left to right shunt. Infusion of 10 micrograms/kg/min nitroprusside over 2 h decreased aortic and left atrial pressures markedly and increased heart rate, whereas systemic, pulmonary, and left to right shunt blood flows hardly changed. Within 30 min after the onset of infusion, the hemodynamic variables stabilized. Aortic and left atrial pressures were still below control levels at that time. The different flows remained the same and heart rate, after an initial fall, increased again. The pattern of hemodynamic changes was not influenced by age or the presence of an aortopulmonary left to right shunt. Based on this study, we do not advocate sodium nitroprusside administration in case of a left to right shunt with normal arterial pressure and systemic blood flow.

Age Factors↗

PubMed1988

Matching between feline left ventricle and arterial load: optimal external power or efficiency.

We tested the hypothesis that the feline left ventricle normally works at optimal external power as opposed to optimal efficiency by (re)analyzing data from five isolated, blood-perfused cat hearts and 39 open-thorax cats. In the isolated hearts, we measured pump function, external steady power, myocardial oxygen consumption, and efficiency. Optimal external power and optimal efficiency were found at different left ventricular outputs (6.94 +/- 0.33 and 8.35 +/- 0.37 ml/s, respectively; P less than 0.001). In the in situ cat hearts the working point was found at an output of 4.72 +/- 0.32 ml/s, whereas optimal external power was found at 4.84 +/- 0.26 ml/s. These values were not significantly different. Assuming that the point of optimal efficiency was located at the same fraction of the maximal unloaded left ventricular output (Fmax) as in the isolated hearts, i.e., 0.7, we found the point of optimal efficiency for the in situ heart at a flow of 5.83 +/- 0.32 ml/s, which was significantly different (P less than 0.001) from the flow in the working point. Our data therefore indicate that the left ventricle in the open-thorax cat is matched to the arterial load such that its external power output rather than efficiency is optimized.

Algorithms↗

PubMed1987

Myocardial blood flow and VO2 in conscious lambs with an aortopulmonary shunt.

We measured myocardial blood flow (QLVFW) and O2 consumption of the left ventricular free wall (VO2, LVFW) in 13 chronically instrumented, 7-wk-old lambs with an aortopulmonary left-to-right shunt (S) and in 10 control lambs without a shunt (C). The measured VO2, LVFW was compared with the calculated values obtained by two predictive indexes, the rate-pressure product (RPP) and the pressure-work index (PWI). Measured VO2, LVFW in S lambs was significantly higher than in C lambs [983 +/- 104 (SE) vs. 475 +/- 57 mumol X min-1 X 100 g LV-1, P less than 0.001]. This was achieved by the significantly higher QLVFW (294 +/- 33 vs. 145 +/- 15 ml X min-1 X 100 g LV-1, P less than 0.002), since the arteriovenous O2 difference across the left ventricular free wall was similar in both groups of lambs. Total coronary blood flow per unit body mass in S lambs was higher than in C lambs (14.1 +/- 1.5 vs. 5.6 +/- 0.6 ml X min-1 X kg-1, P less than 0.001), not only because of the increased VO2, LVFW per unit muscle mass, but also because of the increased total heart weight (102.4 +/- 6.4 vs. 81.2 +/- 4.9 g, P less than 0.02). Correct estimation of VO2, LVFW by means of the RPP and the PWI was only possible in C lambs. In S lambs the estimated values were significantly lower than the measured ones.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Beat-to-beat estimation of peripheral resistance and arterial compliance during pressure transients.

We have used a computer-based parameter estimation method to obtain peripheral resistance, total arterial compliance, and characteristic resistance from the measurement of aortic pressure and flow in the open-thorax cat, assuming the three-element windkessel as a model of the systemic arterial tree. The method can be applied on a beat-to-beat basis in the steady state and in transients. We have validated this method by analyzing nonsteady-state data obtained from an electrical analog with fixed values of the resistances and compliance and by showing that the values obtained by this procedure were within 5% of the fixed values of the circuit. Changes in total peripheral resistance and arterial compliance were studied before, during, and after acute heart rate changes in five open-thorax cats with blocked autonomous nervous system. As expected, the peripheral resistance, estimated during the heart rate transient [3.93 +/- 0.94 (SE) kPa X ml-1 X s] was the same as before the transient (3.53 +/- 0.83 kPa X ml-1 X s); total arterial compliances were also identical (0.28 +/- 0.04 vs. 0.27 +/- 0.03 ml/kPa). In six cats without nervous blockade we obtained similar results. Calculation of peripheral resistance during transients from the mean pressure-to-mean flow ratio, i.e., without correction for arterial compliance, suggested changes in resistance values of less than or equal to 57%, which shows that correction is necessary. The findings indicate that peripheral resistance and total arterial compliance can be estimated in vivo on a beat-to-beat basis, even during hemodynamic transients.

Animals↗

PubMed1987

Comparative circulatory effects of isoproterenol, dopamine, and dobutamine in conscious lambs with and without aortopulmonary left-to-right shunts.

We studied the effect on the circulation of the catecholamines isoproterenol, dopamine, and dobutamine in chronically instrumented lambs with aortopulmonary left-to-right shunts (ages 11 to 87 days) and without shunts (ages 8 to 97 days). Infusion of 0.1 microgram/kg/min isoproterenol or 10 micrograms/kg/min dobutamine markedly increased heart rate and systemic and pulmonary blood flows, while stroke volume and the left-to-right shunt flow did not change. Since pulmonary blood flow increased and the left-to-right shunt flow did not change, the left-to-right shunt fraction decreased with the infusions of isoproterenol and dobutamine. The hemodynamic changes during the infusion of isoproterenol and dobutamine occurred immediately after the start of infusion and stabilized within a few minutes. The pattern of hemodynamic changes was not influenced by the presence of an aortopulmonary left-to-right shunt or by age. Infusion of 10 micrograms/kg/min dopamine caused only small hemodynamic changes. This study shows that heart rate and systemic blood flow in the lamb are closely related. Furthermore, it demonstrates that despite an increased systemic blood flow, left-to-right shunt flow does not change after infusion of isoproterenol and dobutamine. Any decision as to which positive inotropic agent might be preferred at an early age should await experimental work concerning the effect of these agents on the myocardial oxygen demand and on the distribution of the systemic blood flow.

Animals↗

PubMed1985

Enterohepatic circulation in the rat.

Several compounds, in particular bile acids, undergo enterohepatic circulation (EHC). Limited data are available on the pathophysiologic aspects of this circulation. In the present study we describe a surgical technique in rats that allows a long-term, reversible interruption of the EHC and monitoring of peripheral blood levels without direct surgical intervention. This technique excludes the effects of anesthesia and surgical trauma. The model's validity has been tested extensively. We used this animal model to investigate acute and chronic effects of interruption and subsequent restoration of the EHC on (a) nutritional status, (b) plasma cholesterol levels and hepatic cholesterol synthesis, and (c) biliary bile acid, phospholipid, and cholesterol excretion. Interruption of the EHC resulted in an increased food intake and enhanced fecal energy loss, caused by a less efficient intestinal absorption. Plasma cholesterol concentrations declined immediately after the interruption of the EHC, but returned to almost control values during bile diversion. A marked overshoot followed the subsequent restoration of the EHC. Hepatic cholesterol synthesis showed a five-fold increase after 8 days of bile diversion but returned to control values within 2 days after restoration of the EHC. After interruption of the EHC, bile acid, phospholipid, and cholesterol excretion decreased sharply but stabilized after 3 h at 7.6%, 20%, and 23%, respectively, of their initial values. Bile acid output, representing hepatic synthesis, slowly increased over 4 days, but never exceeded 13% of its value during intact EHC. Subsequent restoration of the EHC could rapidly reverse the observed effects of the interruption. The animal model described in the present study is an excellent tool in studying the acute and chronic effects of disturbances of the EHC.

Animals↗