Biomedical subjects

J Dinerman

Publications and source records attributed to J Dinerman.

5 recordsLinked to original sources

PubMed1998

Interaction between neuronal nitric oxide synthase and inhibitory G protein activity in heart rate regulation in conscious mice.

Nitric oxide (NO) synthesized within mammalian sinoatrial cells has been shown to participate in cholinergic control of heart rate (HR). However, it is not known whether NO synthesized within neurons plays a role in HR regulation. HR dynamics were measured in 24 wild-type (WT) mice and 24 mice in which the gene for neuronal NO synthase (nNOS) was absent (nNOS-/- mice). Mean HR and HR variability were compared in subsets of these animals at baseline, after parasympathetic blockade with atropine (0.5 mg/kg i.p.), after beta-adrenergic blockade with propranolol (1 mg/kg i.p.), and after combined autonomic blockade. Other animals underwent pressor challenge with phenylephrine (3 mg/kg i.p.) after beta-adrenergic blockade to test for a baroreflex-mediated cardioinhibitory response. The latter experiments were then repeated after inactivation of inhibitory G proteins with pertussis toxin (PTX) (30 microgram/kg i.p.). At baseline, nNOS-/- mice had higher mean HR (711+/-8 vs. 650+/-8 bpm, P = 0.0004) and lower HR variance (424+/-70 vs. 1,112+/-174 bpm2, P = 0.001) compared with WT mice. In nNOS-/- mice, atropine administration led to a much smaller change in mean HR (-2+/-9 vs. 49+/-5 bpm, P = 0.0008) and in HR variance (64+/-24 vs. -903+/-295 bpm2, P = 0.02) than in WT mice. In contrast, propranolol administration and combined autonomic blockade led to similar changes in mean HR between the two groups. After beta-adrenergic blockade, phenylephrine injection elicited a fall in mean HR and rise in HR variance in WT mice that was partially attenuated after treatment with PTX. The response to pressor challenge in nNOS-/- mice before PTX administration was similar to that in WT mice. However, PTX-treated nNOS-/- mice had a dramatically attenuated response to phenylephrine. These findings suggest that the absence of nNOS activity leads to reduced baseline parasympathetic tone, but does not prevent baroreflex-mediated cardioinhibition unless inhibitory G proteins are also inactivated. Thus, neuronally derived NO and cardiac inhibitory G protein activity serve as parallel pathways to mediate autonomic slowing of heart rate in the mouse.

Animals↗

PubMed1993

Unstable angina: relationship of clinical presentation, coronary artery pathology, and clinical outcome.

Patients with unstable angina are heterogeneous with respect to presentation, coronary artery morphology, and clinical outcome. Subclassification of these patients based on clinical history has been proposed as a means of identifying individuals at increased cardiac risk. We applied such a classification system to 129 patients discharged from a coronary care unit with a diagnosis of acute myocardial ischemia. Patients were then assessed for cardiac events (recurrent angina requiring revascularization, myocardial infarction, death) 12 months following hospital discharge. Patients were classified as recent onset unstable angina preinfarction (n = 42), crescendo unstable angina preinfarction (n = 48), and unstable angina postinfarction (n = 39). Within each of these groups, the patients were further subclassified based on the occurrence of angina on effort, at rest, or both. No attempt was made to subset patients taking anti-ischemic drugs at the time of clinical presentation to the physician. Coronary angiographic pathology (morphology and number of vessels involved) was similar in the subgroups, but coronary artery thrombus was statistically more likely to be found in patients with crescendo rest angina preinfarction or with frequent anginal episodes at rest postinfarction. Mortality was significantly higher for patients with unstable angina postinfarction (7.7%) than preinfarction (1.1%). No statistical differences were noted between the subgroups with respect to the occurrence of myocardial infarction or recurrent unstable angina requiring revascularization. These data suggest that subclassification of unstable angina patients based on clinical characteristics at presentation is not useful to predict subsequent myocardial infarction or recurrent angina requiring revascularization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Neutrophil function in ischemic heart disease.

Neutrophils contribute to the healing of and scar formation in myocardium after ischemic injury. Many recent studies indicate that neutrophils may be involved in the genesis and propagation of myocardial ischemia. To characterize neutrophil function in ischemic heart disease, neutrophil chemotaxis, leukotriene B4 (LTB4) generation, and elastase release in plasma were measured in 20 patients with stable angina, 17 patients with unstable angina or acute myocardial infarction (AMI), and 20 age-matched control subjects. Neutrophils from patients with stable angina exhibited markedly increased chemotactic activity and LTB4 generation as compared with the age-matched control subjects (p less than 0.01). Neutrophils of nine of 17 patients with unstable angina or AMI clumped spontaneously ex vivo and exhibited marked pseudopod formation and granule extrusion on electron microscopy. Subsequent chemotactic activity and LTB4 generation by neutrophils from these patients was less than in patients with stable angina, suggesting previous in vivo activation. Plasma levels of peptide B beta, a product of fibrin degradation by human neutrophil elastase, were approximately 15-fold higher (p less than 0.001) in patients with unstable angina or AMI (588 +/- 171 pmol/l, mean +/- SEM) compared with those in patients with stable angina (37 +/- 25 pmol/l) or control subjects (40 +/- 22 pmol/l), confirming intense in vivo neutrophil activation. Our study shows enhanced neutrophil function in patients with ischemic heart disease. The increased neutrophil chemotactic activity and LTB4 generation may be markers of stable angina pectoris. Intense neutrophil activation in unstable angina or AMI, as manifested by morphologic changes in neutrophils and elastase release, may relate to ongoing in vivo cellular activation.

Chemotaxis, Leukocyte↗

PubMed1988

Enhancement of human neutrophil function by platelets: effects of indomethacin.

To characterize the influence of presence of platelets on human neutrophil function, neutrophil oxidative burst, chemotaxis, leukotriene B4 and prostacyclin generation were examined in the presence of physiologic concentration of platelets (40: 1). Presence of platelets significantly (P less than or equal to 0.05) increased all these neutrophil functions. To determine if cyclooxygenase products are involved in platelet-neutrophil interaction, neutrophils (+/- platelets) were incubated with indomethacin. Although high concentrations of indomethacin (10 microM) inhibited neutrophil (no platelets) chemotaxis and leukotriene B4 generation, these inhibitory effects of indomethacin were attenuated in the presence of platelets. Thus presence of platelets enhances neutrophil activity and overcomes the inhibitory effects of indomethacin on neutrophils.

Blood Platelets↗

PubMed1988

Systemic and coronary hemodynamic effects of prostacyclin and nitroprusside in conscious dogs.

In order to simulate physiologic conditions and eliminate the influence of anesthesia on the cardiovascular responses to prostacyclin (PGI2) and nitroprusside, hemodynamic parameters were monitored in conscious dogs prior to and during infusion of the two agents at equally hypotensive concentrations. Heart rate was significantly increased with nitroprusside (p less than or equal to 0.05) and decreased with PGI2 (p less than or equal to 0.01), while mean ascending aortic blood flow or cardiac output increased (p less than or equal to 0.05) in response to both PGI2 and nitroprusside, more with nitroprusside than with PGI2 (p less than or equal to 0.05). Stroke volume increased with PGI2 only (p less than or equal to 0.05 vs. control, p less than or equal to 0.05 vs. nitroprusside). Both systemic and coronary (circumflex) vascular resistances decreased more with nitroprusside than with PGI2 (p less than or equal to 0.05); however, characteristic impedance (index of aortic elasticity) decreased similarly with PGI2 and nitroprusside. Circumflex coronary blood flow increased (p less than or equal to 0.05) only with nitroprusside. These results indicate that in conscious dogs (a) nitroprusside causes a greater decrease in vascular (systemic and coronary) resistance compared to PGI2, but the effects of the two vasodilators on arterial distensibility are similar; (b) nitroprusside, but not PGI2, causes a marked increase in coronary blood flow; and (c) the major distinguishing hemodynamic response to these vasodilators relates to marked bradycardia with PGI2 and tachycardia with nitroprusside, which may account for the observed differences in aortic blood flow and stroke volume.

Animals↗