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Biomedical subjects

H Feinberg

Publications and source records attributed to H Feinberg.

At least 73 records · Page 4Linked to original sources
PubMed1984

Antagonism of thromboxane A2/prostaglandin H2 by 13-azaprostanoic acid prevents platelet deposition to the de-endothelialized rabbit aorta in vivo.

The present study evaluated the direct involvement of thromboxane A2/prostaglandin H2 (TXA2/PGH2) in the process of thrombus formation at a site of vascular damage. De-endothelialization of the rabbit aorta was performed by a balloon catheter technique. Platelet deposition to the injured vessel was measured using 111Indium-labeled autologous platelets. Studies using the radiolabeled TXA2/PGH2 antagonist, 13-azaprostanoic acid (13-APA), indicated that 13-APA has an in vivo half-life of approximately 35 min and is excreted by the kidney in the metabolized form. Addition of 13-APA to rabbit plasma samples in vitro produced a dose-dependent inhibition of arachidonic acid-induced platelet aggregation. When comparable plasma levels of 13-APA were achieved by infusion of 13-APA (300 micrograms/kg/min for 90 min), a similar dose-dependency of inhibition of ex vivo aggregation was observed. Furthermore, at a plasma concentration of 40 microM, 13-APA was found to inhibit platelet deposition to the de-endothelialized rabbit aorta by 45%. Because 13-APA does not interfere with arachidonic acid metabolism, the ability of 13-APA to suppress thrombus formation is presumably due to direct antagonism of TXA2/PGH2 at the platelet receptor level. These findings, therefore, provide evidence that TXA2 and/or PGH2 have a major role in platelet deposition at a site of vascular damage.

Animals↗
PubMed1984

Optimal intraoperative protection of myocardium distal to coronary stenoses.

Metabolic evidence of improved delivery of cardioplegic solutions by adjuvant use of nitroglycerin (NTG) and reinfusing these solutions distal to an obstructed coronary artery was sought in 40 dogs subjected to cold cardioplegic arrest. The left anterior descending coronary artery was occluded prior to initiating arrest by intra-aortic root infusion. Cardioplegic solution was reinfused with the left anterior descending occluded throughout ischemia (Group I), or with this artery reopened, to simulate a completed distal anastomosis (Group II). Serial biopsy specimens of the left ventricular apex were assayed for adenosine triphosphate and creatine phosphate, while specimens from the posterior left ventricular wall served as controls. Regional myocardial temperatures were recorded throughout ischemia. Half of the hearts in each group received 300 micrograms of nitroglycerin in the cardioplegic solution. Adenosine triphosphate was preserved in myocardium distal to a patent coronary artery whether nitroglycerin was added to the cardioplegic solution or not (control, control + NTG). Moreover, nitroglycerin did not prevent the 26% to 34% (p less than 0.05) decline in adenosine triphosphate levels when the left anterior descending remained obstructed throughout ischemia (Group I, I + NTG). However, opening the left anterior descending for reinfusion of cardioplegic solution allowed adenosine triphosphate to be preserved at end-ischemia (Group II, II + NTG). In addition, the metabolic reperfusion injury manifested by a 37% (p less than 0.01) decline in adenosine triphosphate levels after aortic unclamping (Group II) was obviated when nitroglycerin was added to the cardioplegic solution delivered in this manner (II + NTG). The depletion of cardioplegic solution stores during ischemia was more severe in the experimental groups than in controls (p less than 0.05). These metabolic changes did not correlate with regional myocardial temperature gradients. The data indicate that myocardium jeopardized by coronary stenoses can be preserved as well as myocardium supplied by a patent coronary artery by adjuvant use of nitroglycerin and varying the mode of delivery of the cardioplegic solution.

Adenosine Triphosphate↗
PubMed1983

Chlorpromazine inhibits loss of contractile function, compliance and ATP in ischemic rabbit heart.

Using a modified Langendorff preparation, rabbit hearts were either continuously perfused at 37 degrees C for 150 min, in the presence of O2 and substrate, or after a 30 min equilibration period exposed to global ischemia followed by 30 min of reperfusion. Ischemia, for 90 min at 27 decrees C or for 60 min at 37 degrees C was compared. Perfusion pressure, heart rate, and ventricular volume were maintained constant. Contractile function and metabolic status were assessed. The effect of chlorpromazine, administered (30 mg/kg IP) 30 min prior to sacrifice, was compared to the untreated animal. (1) Chlorpromazine had little effect on the contractile function or metabolic status of hearts continuously perfused for 150 min in the presence of O2 and substrate. (2) The chloropromazine-treated hearts maintained contractile function and metabolic status at preischemic levels following exposure to 90 min of global ischemia at 27 degrees C and reperfusion at 37 degrees C. Untreated hearts exhibited a severe deterioration in both contractile and metabolic parameters under the same conditions. Both untreated and chlorpromazine-treated hearts exhibited loss of contractile function after 60 min ischemia at 37 degrees C; untreated hearts had undetectable ATP levels while chlorpromazine-treated hearts exhibited low levels of ATP. (3) Untreated hearts, exposed to 90 min of ischemia at 27 degrees C, exhibited a significant loss in compliance, while the compliance of chlorpromazine-treated hearts was unchanged from pre-ischemic levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1983

Prevention and reperfusion injury following cardioplegic arrest by pulsatile flow.

To assess the efficacy of pulsatile flow in minimizing reperfusion injury following cardioplegic arrest, 20 dogs supported by cardiopulmonary bypass underwent 60 minutes of hypothermic, hyperkalemic crystalloid cardioplegic arrest. The effects of pulsatile flow (Group 2), initiated during 30 minutes of reperfusion, on myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) stores, coronary blood flow, and myocardial water content were compared with the effects of linear flow reperfusion (Group 1). Myocardial ATP stores were maintained at preischemic levels by this mode of myocardial protection. However, pulsatile flow prevented the significant decline in ATP levels incurred during linear reperfusion. Creatine phosphate stores, although depleted during arrest, were restored equally, regardless of the mode of reperfusion. The decline in ATP stores was associated with no pathological increase in myocardial water content, but was associated with persistent reactive hyperemia. In contrast, after 30 minutes of pulsatile reperfusion, coronary blood flow was significantly decreased compared with preischemic flow. These data indicate that pulsatile reperfusion can prevent the unique decline in ATP levels associated with the restoration of coronary flow after cardioplegic arrest (reperfusion injury), and support its continuing evaluation as an adjunct to adequate intraoperative myocardial protection.

Adenosine Triphosphate↗
PubMed1983

Beneficial metabolic effect of nucleoside augmentation on reperfusion injury following cardioplegic arrest.

Restoration of coronary flow after hyperkalemic cardioplegic arrest (HCA) is associated with a unique metabolic reperfusion injury (RI) manifested by declining nucleotide stores despite their end-ischemic preservation. Prevention of this RI by exogenous provision of adenosine with or without inhibition of adenosine's major catabolic enzyme was assessed in 27 dogs subjected to 60 minutes of HCA. The effect of aortic root infusion of 40 mg/kg of adenosine in addition to adenosine deaminase inhibition by 10 mg/kg of EHNA (group 2) initiated during 60 minutes of reperfusion on myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) stores and coronary blood flow (CBF) were compared to animals having adenosine infusion alone (group 3) or controls (group 1). Although ATP levels were preserved at the end of HCA in all groups, adenosine infusion with or without EHNA prevented the significant 23 percent decline in ATP stores incurred during unmodified reperfusion (p less than 0.01, group 1). The CP stores decreased (p less than 0.05, all groups) during arrest, but were restored to preischemic levels during reperfusion. When measured 60 minutes after aortic unclamping, CBF was 312 percent of preischemic flow in group 3 (p less than 0.01), only 170 percent in group 2 (p less than 0.05), and unchanged in controls (group 1). The data indicate that provision of adenosine as a nucleotide precursor prevents the metabolic RI following HCA. In addition, inhibition of adenosine catabolism is not necessary for this salutary effect, nor is adenosine's efficacy solely mediated by augmentation of CBF.

Adenine↗
PubMed1983

Induction of cardioplegia with blood and crystalloid potassium solutions during prolonged aortic cross-clamping.

Recent controversy concerns the proper vehicle for delivery of potassium cardioplegia. In the present study, adult dogs supported by cardiopulmonary bypass were subjected to 2 hours of multidose, hypothermic potassium cardioplegic arrest with 30 minutes of reperfusion with either autologous blood or crystalloid solution as the cardioplegic vehicle. Preservation of myocardial high-energy nucleotide stores was assessed by serial left ventricular biopsies assayed for adenosine triphosphate (ATP) and creatine phosphate. Preischemic and postischemic ventricular function was assessed by the use of an isovolumic intraventricular balloon. ATP stores were equally maintained at preischemic levels after ischemia and reperfusion by both autologous blood and crystalloid solution. Although creatine phosphate stores significantly declined (P less than 0.01, both groups) after 2 hours of arrest, reperfusion allowed equal restoration of preischemic levels. Maximum first derivative of left ventricular pressure and measured velocity were not depressed by either mode of protection. Similarly, myocardial compliance, as assessed by length-tension curves, showed no change following either autologous blood or crystalloid solution. The data show equal and significant myocardial protection by multidose, hypothermic potassium cardioplegia when both delivery vehicles were used.

Animals↗
PubMed1983

Cardioplegia does not prevent reperfusion injury induced by intracoronary platelet deposition.

We have shown that after global myocardial ischemia, reperfusion injury may be related to platelet deposition in the coronary microcirculation. The purpose of this study was to determine whether multidose hypothermic potassium cardioplegia suppresses platelet deposition during postischemic reperfusion. Platelets labeled with 111In and erythrocytes labeled with 51Cr were injected into dogs subjected to either 120 min of continuous cardiopulmonary bypass (control, n = 4), 60 min of global normothermic myocardial ischemia followed by 50 min of reperfusion (n = 6), or global ischemia with cardioplegia (n = 5). Intracoronary platelet deposition was determined by comparing the double-labeled isotope activity of myocardial biopsy specimens to peripheral blood. Reperfusion after global myocardial ischemia resulted in substantial deposition of platelets within the coronary vasculature in both the cardioplegia-treated (215 +/- 40 platelets/mg) and untreated (269 +/- 95 platelets/mg) groups. These increases were significantly greater than those measured during continuous bypass (48 +/- 2 platelets/mg; p less than .01). Cardioplegia, despite apparent washout of the microcirculation, does not alter platelet deposition. Thus other platelet-stabilizing measures must be used to prevent platelet deposition-induced reperfusion injury after surgical global ischemia.

Animals↗
PubMed1982

Pulsatile reperfusion does not modify global myocardial ischemic injury.

In an attempt to arbitrate the reputed clinical efficacy of pulsatile flow during reperfusion in minimizing ischemic injury, 32 mongrel dogs supported by normothermic cardiopulmonary bypass were subjected to 30 minutes (Groups IC and IP) or 60 minutes (Groups IIC and IIP) of global myocardial ischemia. The effect of pulsatile flow (P) initiated during 30 minutes of reperfusion on the recovery of myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) stores, coronary blood flow, and myocardial water content (MWC) was compared to the effect of linear reperfusion (C) in another group of animals. ATP stores, which significantly decreased to 43% and 53% of preischemic levels (Groups IC and IP, respectively, p less than 0.01) and 36% and 31% of control values (Groups IIC and IIP, respectively. p less than 0.001), did not increase with either pulsatile or linear reperfusion. CP stores, depleted 97% during ischemia in all groups, returned to preischemic levels regardless of the mode of reperfusion flow. Coronary blood flow measured 30 minutes after aortic unclamping was not significantly different from control flow in any group. MWC significantly decreased during ischemia from 80.5% +/- 0.8% to 76.5% +/- 1.1% in Group IC and from 81.8% +/- 1.2% to 76.8% +/- 0.8% in Groups IP (p less than 0.05) and returned to preischemic levels with reperfusion. However, following 60 minutes of ischemia, pulsatile reperfusion prevented the significant increase in MWC that accrued after linear reperfusion (80.7% +/- 1.5% to 84.0% +/- 0.7%, p less than 0.05). These data indicate that pulsatile reperfusion initiated after an ischemic injury that results in a 50% or greater depletion of myocardial ATP stores does not restore myocardial nucleotide levels or enhance coronary blood flow, although the pathological increase in MWC may be avoided.

Adenosine Triphosphatases↗
PubMed1982

Platelet deposition after surgically induced myocardial ischemia. An etiologic factor for reperfusion injury.

Despite meticulous adherence to presently known principles of myocardial preservation, reperfusion after aortic cross-clamping results in a unique injury manifested by decreasing high-energy phosphate levels and increased coronary resistance. We hypothesize that platelet deposition into the coronary microvasculature is a major factor in reperfusion injury. To differentiate platelet deposition due to subendocardial hemorrhage from deposition due to vascular entrapment, we infused 111In-labeled platelets together with 51Cr-labeled erythrocytes into 15 dogs that were on normothermic bypass and subjected to 60 minutes of global ischemia followed by 30 minutes of reperfusion. Platelet deposition is indicated only when the proportion of platelets to erythrocytes in tissue exceeds that measured by peripheral blood. Myocardial biopsy specimens were obtained after 10 minutes of bypass, 120 minutes of continuous bypass (Group I), and at the end of reperfusion after global ischemia (Group II). In five dogs (Group III), dipyridamole (1 mg/kg), an antiplatelet activation agent, was administered in the preischemic period. Platelet deposition was expressed as the number of radioactive-labeled platelets deposited per gram of tissue. Bypass for 120 minutes resulted in only a minimal increase in platelet deposition. However, normothermic ischemia followed by reperfusion resulted in over a twofold increase in platelet deposition compared to controls. Pretreatment with dipyridamole appeared to avoid platelet deposition. These data indicate that platelet deposition in the coronary microcirculation following surgically induced myocardial ischemia may be associated with reperfusion injury and that antiplatelet drugs after this sequence.

Animals↗
PubMed1980

Movement of sodium into human platelets.

Addition of ADP induces platelets in plasma to undergo shape change from a disc to a spiny sphere and to develope adhesiveness, i.e. to aggregate. The aggregation of human platelets by ADP is associated with a net uptake of Na+. The present experiments demonstrate that the induction of shape change by ADP in acidified or EGTA-treated plasma conditions which inhibit aggregation, is also associated with a movement of Na+ into platelets. When ADP-induced platelet shape change and aggregation is inhibited by prostaglandin E1 Na+ uptake is also blocked. Platelets aggregated by epinephrine do not take up Na+. In a manner analogous to the effect of ADP, polylysine also induces Na+ uptake during aggregation. Vasopressin, in a manner analogous to epinephrine, induces aggregation without Na+ uptake. The increase in platelet Na+ resulting from ouabain inhibition of Na+ efflux induces an increase in the aggregation response to ADP and to epinephrine.

Biological Transport↗
PubMed1980

Effect of dipyridamole on ischemia-induced changes in cardiac performance and metabolism.

The effect of the coronary vasocilator agents dipyridamole and nifedapine on ischemia-induced changes in cardiac performance and coronary flow was studied in extra-corporeal-circulation supported, open-chest dogs during cardio-pulmonary bypass. Coronary flow and isovolumic cardiac performance were measured prior to clamping the aorta to induce global ischemic for 60 min and again after 30 min of reperfusion. Both agents given prior to ischemia significantly enhanced the coronary flow measured 30 min after reperfusion. Almost complete complete return of pre-ischemic left ventricular dp/dt and diastolic compliance was seen if dipyridamole was administered prior to the onset of ischemia. Dipridamole administered at the end of the ischemic period and prior to reperfusion also prevented the ischemia-induced fall in dp/dt but not the decrease in compliance. Myocardial high energy phosphate compounds decreased markedly during global ischemia and dipyridamole administration had no effect on the rate or extent of their depletion. Nifedapine administration led to even greater post-ischemic coronary vasodilation; however, the ischemia-induced decline in myocardial performance was not prevented.

Animals↗
PubMed1980

Pyridoxal phosphate inhibition of platelet function.

The effect of pyridoxal phosphate (PLP) on human platelet function in vitro was studied. PLP inhibited adenosine diphosphate (ADP)-induced shape change, aggregation, and the potentiation by ADP of arachidonic acid-induced aggregation. This inhibition could easily be reversed by increasing concentrations of ADP or by removing PLP. The addition of sodium borohydride to PLP-treated platelets produced an irreversible inhibition of ADP aggregation. Thus it is possible that PLP inhibited ADP-induced platelet function by forming a Schiff base with platelet-surface amino groups. PLP also produced a partial inhibition of platelet aggregation to epinephrine, arachidonic acid, A23187, and a dose-dependent inhibition of [14C]serotonin release to epinephrine and arachidonic acid. PLP did not inhibit [14C]serotonin release to A23187, nor did it suppress arachidonic acid-induced malondialdehyde production. The conclusion is drawn that the partial inhibition by PLP of platelet aggregation observed to epinephrine, arachidonic acid, and A23187 resulted from PLP's inhibition of the effect of released ADP.

Adenosine Diphosphate↗
PubMed1980

Epinephrine induces Ca2+ uptake in human blood platelets.

Human blood platelets isolated by albumin density gradient centrifugation take up Ca2+ during 10(-6)M epinephrine-induced primary aggregation but not during 10(-6)M ADP-induced primary aggregation. Platelet uptake of Ca2+ is dose-dependent over a range of 10(-7) to 10(-5) M epinephrine. Antagonism of the platelet alpha-receptor by phentolamine (10(-6)M) results in inhibition of both epinephrine-stimulated Ca2+ uptake and aggregation. The Ca2+ antagonist verapamil (50 micro M) blocks Ca2+ uptake and epinephrine-induced aggregation, but not ADP-induced aggregation. The verapamil inhibition of aggregation is reduced on Ca2+ addition. These results suggest that epinephrine acts to stimulate primary platelet aggregation through a specific receptor interaction that results in a selective increase in platelet membrane permeability to Ca2+.

Adenosine Diphosphate↗