Biomedical subjects

B Chandel

Publications and source records attributed to B Chandel.

10 recordsLinked to original sources

PubMed1997

Pharmacologic stress-induced regional myocardial blood flow heterogeneity and left ventricular wall thickening abnormality: comparison of intravenous adenosine with dipyridamole in a model of critical coronary stenosis.

Variations in reported sensitivity of myocardial perfusion scans or wall motion abnormalities during pharmacologic stress with intravenous adenosine and dipyridamole may be caused by differences in myocardial oxygen demand or myocardial blood flow redistribution induced by each agent. To investigate the physiologic correlates of functional abnormalities during pharmacologic stress testing, regional myocardial blood flow (radiolabeled microsphere technique) and left ventricular segmental wall thickening (quantitative two-dimensional echocardiography) were measured in 9 dogs with an open chest model of critical stenosis of the left circumflex coronary artery. Data were obtained at baseline and peak drug infusion for intravenous adenosine (0.42 mg/kg over a 3-minute period) and for intravenous dipyridamole (0.56 mg/kg over a 4-minute period). Adenosine and dipyridamole induced regional flow abnormality in 7 (77%) of 9 dogs. Myocardial segments with decreased endocardial/epicardial flow ratio were similar for both agents (2.9 +/- 1.8 vs 2.7 +/- 1.3, p = [NS]). Segments with myocardial flow heterogeneity (ratio of endocardial flow to control left anterior descending/left circumflex endocardial flow) were similar for both agents (2.7 +/- 0.9 vs 2.3 +/- 1.0, p = NS). Adenosine-induced wall thickening abnormality (77% vs 55% with dipyridamole) correlated with regional flow abnormality. Significantly lower mean arterial pressure (53 +/- 1.7 mm Hg vs 64 +/- 1.9 mm Hg, p < 0.01) and more prolonged drug effect (18 +/- 6.4 min vs 3 +/- 1.4 min, p < 0.001) were seen for dipyridamole compared with adenosine. Adenosine induces regional flow abnormality similar to dipyridamole but with less hemodynamic perturbation, and adenosine-induced wall thickening abnormality more closely parallels regional flow abnormality.

Adenosine↗

PubMed1995

Evidence for a colonic PAF receptor.

We sought to determine the effect of exogenously administered platelet-activating factor (PAF) on eicosanoid release from the left colon of the rabbit. Using an isolated buffer-perfused rabbit left colon preparation, 1.0- or 5.0-micrograms doses of PAF were infused into the inferior mesenteric artery. Effluents from the inferior mesenteric vein and colonic lumen were collected and the concentrations of the eicosanoids, prostaglandin E, 6-ketoprostaglandin F1 alpha, thromboxane B2, and leukotriene B4 (LTB4), were measured by ELISA. During PAF infusion there was a significant increase of all prostanoids, but not LTB4 into the venous effluent and colonic luminal perfusate when compared to control experiments. Additional studies were performed by pretreating the colons with the PAF antagonists WEB-2170 or alprazolam prior to PAF infusion. Both venous and luminal effluent prostanoid release was effectively blocked by WEB-2170, but not by alprazolam. Colons pretreated with WEB-2170 prior to PAF had markedly diminished tissue injury when compared to colons treated with PAF alone. Inhibition of PAF-stimulated prostanoid release by WEB-2170 suggests that a PAF-sensitive receptor is present in rabbit colonic tissue which may induce eicosanoid-mediated tissue injury.

Animals↗

PubMed1995

MEGX (monoethylglycinexylidide): a novel in vivo test to measure early hepatic dysfunction after hypovolemic shock.

A quantitative liver test based on the formation of the lidocaine metabolite monoethylglycinexylidide (MEGX), was used to evaluate the effect of hemorrhagic shock at 40 mmHg for 90 min on Sprague-Dawley rats. After 2 h of stabilization, lidocaine was injected (2 mg/kg). A second group received volume resuscitation with Ringer's lactate over 1 h (15 mL/kg) after shock, and after 1 h of stabilization lidocaine was administered. These groups were compared to control animals. Blood samples were drawn at 0 time (baseline), prior to lidocaine injection, and at 10, 15, 30, and 60 min after lidocaine injection. MEGX values in shocked animals were significantly lower than in the control group; in animals receiving volume resuscitation, levels were higher than the shocked animals without resuscitation, but did not reach control levels. Thus, shock produced a significant depression of hepatocyte function, which was partially reversed by Ringer's lactate resuscitation. The MEGX test appears to be a suitable tool for clinical evaluation and therapeutic intervention after shock.

Animals↗

PubMed1994

Effect of platelet-activating factor and its antagonists on colonic dysmotility and tissue levels of colonic neuropeptides.

We investigated whether platelet-activating factor (PAF) alters colonic tissue levels of substance P and vasoactive intestinal peptide (VIP), two neuropeptides that regulate colonic motility. Left colons were harvested from NZ White Rabbits and underwent vascular perfusion via the inferior mesenteric artery. Strain gauge transducers were sewn onto the serosal surface of the colon to evaluate colonic motility. Colons were perfused with either buffered saline alone or with 5.0 x 10(-5) M PAF. PAF administration increased tissue VIP and substance P levels and decreased the force of colonic contractions. Pretreatment with WEB-2170 or alprazolam decreased concentrations of both tissue neuropeptides, and decreased the force of colonic contractions and minute motility index. These results suggest that both VIP and substance P are stimulated by PAF and may participate in colonic dysmotility during inflammatory states.

Alprazolam↗

PubMed1994

The effect of Clostridium difficile toxin on colonocyte prostanoid activity.

Antibiotic-associated colitis is caused by Clostridium difficile toxin. However, the pathophysiology of this entity is poorly understood. The aim of this study was to determine the effects of C. difficile toxin on colonocyte cyclooxygenase and phospholipase A2 (PLA2) activity. A transformed colonocyte cell line (Caco-2) was grown to confluency on 6 well plates. The cells were stimulated with graded concentrations of C. difficile toxin. In separate experiments, the cells were pretreated for one hour prior to stimulation with the cyclooxygenase inhibitor, indomethacin, or the glucocorticoid, dexamethasone. The culture media was collected one hour following C. difficile stimulation. Prostaglandin E2 (PGE2), 6-keto prostaglandin F1 alpha (6KPGF), thromboxane B2 (TxB2) and leukotriene B4 (LTB4) levels were determined in the media by an ELISA. Platelet activating factor (PAF) concentration was determined by a RIA. C. difficile toxin stimulated PGE2 and 6KPGF levels in a dose dependent fashion but failed to stimulate TxB2, LTB4 or PAF. Prostanoid production was inhibited by indomethacin dose dependently but was not inhibited by dexamethasone. The presence of indomethacin resulted in production of PAF. Our results show that the effects of C. difficile toxin on colonocytes are mediated by cyclooxygenase activity. The increase in PAF formation associated with indomethacin administration suggests that the prostanoids modulate PLA2 activity and inhibit PAF formation.

6-Ketoprostaglandin F1 alpha↗

PubMed1994

A noninvasive method for monitoring cerebral perfusion during cardiopulmonary resuscitation.

PURPOSE: This study evaluates the use of transcranial Doppler (TCD) ultrasound in assessing the changes experienced by the cerebral circulation during cardiopulmonary resuscitation (CPR) and compares it with measurements of internal carotid artery (ICA) flow rates (ultrasonic flow-meter measurements) and cerebral blood flow (CBF) (radioactive-microsphere measurements) in a porcine cardiac arrest model undergoing closed chest CPR. METHODS: Sixteen piglets were anesthetized and subjected to TCD monitoring, ICA flow-rate measurements, and CBF measurements during CPR following induction of ventricular fibrillation. A total of 14 comparisons between TCD and CBF measurements, and 36 comparisons between TCD and ICA flow measurements were performed. Correlations were determined using Pearson's method, and the validity of the correlation was determined using Bonferoni's adjusted probabilities. RESULTS: The correlation between mean cerebral blood flow velocity and mean total ICA flow rate was 0.67 (P < .01). The correlation between peak systolic blood flow velocity and CBF was 0.76 (P = .02). CONCLUSIONS: TCD can provide on-line information about cerebral perfusion during CPR.

Animals↗

PubMed1994

Platelet-activating factor mediates trinitrobenzene induced colitis.

Platelet-activating factor (PAF) is an endogenous phospholipid which may be an important mediator of shock and inflammation. Recent evidence suggests that PAF plays a role in the development of ischemic colitis and inflammatory bowel disease. Its effects are mediated by second messengers, including the arachidonic acid metabolites. Using an ex vivo isolated left colon rabbit perfusion model, our aims were to determine whether exogenously administered trinitrobenzene sulfonic acid (TNB), which produces experimental colitis, stimulates both PAF and eicosanoid release in the colon, and if so, whether this effect can be blocked by a PAF antagonist. Colonic inflammation was induced by the intracolonic administration of 0.25 ml of 50% ethanol containing 30 mg of TNB. Tissue and perfusate concentrations of the eicosanoids, [prostaglandin E (PGE2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TXB2), leukotriene B4 (LTB4)] and the autocoid PAF were measured by ELISA. During TNB infusion there was a significant increase in tissue levels of PAF compared to control colons. Additional studies performed pretreating the colons with the PAF receptor antagonist WEB-2170 prior to TNB infusion blocked PAF release. TNB stimulated release of luminal eicosanoids except LTB4 and suppressed release of tissue prostanoids. Pretreatment with WEB-2170 prior to TNB inhibited luminal eicosanoids, and inhibited PGE2 and prostacyclin, but not TX tissue suppression. Inhibition of TNB-stimulated PAF release by WEB-2170 suggests that PAF may play a role in TNB-induced colitis and this phenomenon may mediate tissue injury.

6-Ketoprostaglandin F1 alpha↗

PubMed1992

The effect of shock on blood oxidation-reduction potential.

Oxidation-reduction (redox) potential measurements were made in the blood of rabbits subjected to hemorrhagic shock followed by treatment with a mild oxidizing agent (albumin). Control redox potential reading corrected for pH was -8.8 +/- 1.3 millivolts (mV) in arterial blood (A) and -18.0 +/- 2.0 mV in venous blood (V). This A-V difference indicated that hydrogen equivalents coming from muscle and other tissues were partially consumed in the lungs. A 20-mV drop on the V and a 13 mV on the A side was seen after shock. This did not fully return to control 2 h after return of the shed blood. Infusion of 2 g of albumin/kg/h raised the V redox potential to control, but it returned to untreated levels when the albumin was discontinued. The reductive load imposed on the animal by shock appeared to be large and not readily reversed by reperfusion or by the quantity of albumin given. Thus, it may be concluded that cellular respiration had not been adequately restored. This reductive load may impede recovery by suppression of cellular respiration and other cell and organ functions.

Animals↗

PubMed1992

Correlation of end-tidal CO2 to cerebral perfusion during CPR.

STUDY OBJECTIVE: A number of studies have demonstrated a correlation between end-tidal carbon dioxide (ETCO2), cardiac output, and return of spontaneous circulation in experimental animals and in patients undergoing closed-chest CPR. Our study attempted to correlate ETCO2 to cerebral blood flow during cardiac arrest. DESIGN: Sixteen piglets were anesthetized, intubated, and instrumented for cerebral blood flow studies. An ultrasonic flow probe was placed on both internal carotid arteries for continuous flow measurements. The animal was fibrillated, and closed-chest CPR was begun. Continuous ETCO2 measurements were obtained and compared with simultaneous internal carotid, cardiac output, and cerebral blood flow measurements. MEASUREMENTS AND MAIN RESULTS: Correlations between ETCO2 and carotid and cerebral blood flow were determined using Pearson's method. The correlation between ETCO2 and total internal carotid flow was .58 (P = .01, Bonferroni's adjusted P = .30). Correlation between ETCO2 and cerebral blood flow was .64 (P = .01, Bonferroni's adjusted P = .09). A partial correlation coefficient for ETCO2 versus cardiac output was .70, whereas it was only .30 for ETCO2 versus cerebral blood flow. CONCLUSION: Partial correlation coefficients suggest that ETCO2 correlates with cerebral blood flow when changes in cerebral blood flow parallel changes in cardiac output.

Animals↗

PubMed1992

Pyrimidine-enhanced purine uptake in hepatocytes and improved survival from hypovolemic shock.

To assess the effect of pyrimidines on the incorporation of purines into rat hepatocytes, monolayer preparations of hepatocytes were incubated with radiolabeled precursors and their uptake determined. The uptake of purine precursors (inosine monophosphate, inosine, and hypoxanthine) was 27.8 +/- 1.31 nmoles per well, per 30 min. In the presence of added pyrimidines (uridine monophosphate, uridine, and orotate), this increased by 22%. Further enhancement (45%) was observed when L-dihydroxyphenylalanine (L-DOPA) plus pyridoxal-5'-phosphate was added to the purine/pyrimidine incubation medium. The effect of increased uptake of purines on survival after hypovolemic shock was also studied. Rats were bled to a blood pressure of 40 mmHg for 105 min and then treated with return of shed blood plus saline with or without purines and pyrimidines. Survival at 24 hr was 43% (15/35) in control animals, 66% (8/12) (P = 0.276) when treated with inosine monophosphate (IMP) and aspartate (60 mumoles/kg each), and 83% (10/12) (P = 0.037) for IMP with aspartate and orotate treatment (60 mumoles/kg each). Thus, the addition of orotate enhanced survival possibly by promoting salvage or by uptake of purines. Nucleotide concentrations in the livers of animals after shock which had received IMP and orotate demonstrated a return of both ATP and energy charge to normal, further indicating the value of this treatment.

Adenosine Diphosphate↗