Biomedical subjects

B G Hook

Publications and source records attributed to B G Hook.

25 records · Page 2Linked to original sources

PubMed1991

Paced beats following single nonsensed complexes in a "codependent" cardioverter defibrillator and bradycardia pacing system: potential for ventricular tachycardia induction.

Patients with implantable defibrillators often require bradycardia pacemakers. Adverse interactions between separate defibrillator and bradycardia pacing units have occurred, including failure to detect ventricular fibrillation due to persistent bradycardia pacing during the arrhythmia. A device with combined bradycardia pacing and antitachycardia therapy capability may obviate adverse device interactions. We describe a previously unrecognized phenomenon that may occur in a combined device when the algorithms for sensing bradycardia and tachycardia are "codependent"; that is, the circuitry for brady- and tachyarrhythmia detection relies on the same automatic gain sense amplifier. Three of 37 patients in whom the device was implanted had ventricular tachycardia initiated when bradycardia pacing stimuli were delivered by the device after probable nonsensed sinus beats. In each case, nonsensed beats appeared to have a markedly diminished amplitude, occurred after ventricular premature depolarizations that produced large amplitude electrograms, and had an electrogram morphology that matched that of sinus rhythm. In each case, the bradycardia pacing interval was at least 1,200 msec (range 1,200 to 1,714 msec). In two of the three patients, large amplitude ventricular premature depolarizations or nonsustained ventricular tachycardia caused an adjustment of the gain control that potentiated the failure to sense the subsequent lower amplitude signal. In all three patients, the induced arrhythmia was rapidly terminated by pacing or cardioversion. Decreasing the bradycardia pacing interval by 110-514 msec has prevented recurrence during short-term follow-up. Our findings suggest that codependent bradycardia and antitachycardia devices may have their own unique potential difficulties in adapting to rapid changes in rate and signal amplitude.

Aged↗

PubMed1986

Reduction of myocardial infarct size by neutrophil depletion: effect of duration of occlusion.

Experiments were performed in the dog to examine the effects of neutropenia on ultimate infarct size resulting from short (90 minutes) or prolonged (4 hours) circumflex coronary artery occlusion. Sheep antiserum to canine neutrophils was used to produce neutropenia. Control animals received nonimmune serum. Neutrophil infiltration into myocardial infarcts was examined using histopathologic techniques and a semiquantitative scoring system. In 90-minute occlusions with 24-hour reperfusion, neutropenia was associated with the development of significantly smaller infarcts: normopenic group, 43.2% +/- 3.3% (n = 7) vs. neutropenic group, 26.6% +/- 3.7% (n = 10) of the area at risk, means +/- SEM. However, in 4-hour occlusion with 6-hour reperfusion experiments, the tendency of neutrophil depletion to reduce infarct size did not reach statistical significance (46.4% +/- 7.2% vs. 31.5% +/- 6.0% of the area at risk, normopenic vs. neutropenic) despite differences in neutrophil infiltration into the reperfused region. The observed differences in ultimate infarct size could not be attributed to differences in myocardial oxygen consumption. The results suggest that a significant amount of myocardial infarction induced by a limited duration of coronary artery occlusion followed by reperfusion is neutrophil dependent and appears to be less important in determining the fate of myocardium subjected to more prolonged periods of ischemia followed by reperfusion.

Agranulocytosis↗

PubMed1983

Reduction of the extent of ischemic myocardial injury by neutrophil depletion in the dog.

Accumulation of polymorphonuclear neutrophils during the acute inflammatory response may exacerbate tissue injury through the release of activated oxygen products or proteolytic enzymes or both. To assess the role of neutrophils in acute myocardial infarction, circulating neutrophil levels in dogs were reduced by 77 +/- 2% (mean +/- SEM) by administering rabbit antiserum to dog neutrophils. Acute myocardial infarction was induced in open-chest anesthetized dogs by 90 minutes of left circumflex coronary artery occlusion followed by 6 hours of reperfusion. Dogs treated with neutrophil antiserum (n = 8) developed myocardial infarcts that were an average of 43% smaller than infarcts in dogs treated with nonimmune rabbit serum (n = 7) (27.0 +/- 4.5% vs 47.1% +/- 7.5% of the area at risk, p less than 0.05). In a saline-treated control group (n = 8), infarct size was 48.0 +/- 4.7% of the area at risk, a value not significantly different from that of the nonimmune serum group but significantly greater than that in the neutrophil antiserum dogs (p less than 0.05). There were no major hemodynamic differences between groups. Histopathologic examination revealed that infarcted myocardium from dogs given saline or treated with nonimmune serum had a substantial neutrophilic infiltrate, which was virtually absent in infarcted tissue from dogs treated with neutrophil antiserum. These observations suggest that neutrophil accumulation in response to myocardial ischemia may be responsible for a substantial portion of the irreversible myocardial injury resulting from temporary coronary artery occlusion.

Agranulocytosis↗

PubMed1983

Potentiation of the antithrombotic effect of prostacyclin by simultaneous administration of aminophylline in a canine model of coronary artery thrombosis.

The antithrombotic efficacy of prostacyclin (PGI2) when administered in conjunction with the phosphodiesterase inhibitor aminophylline was evaluated in a canine model in which coronary artery thrombosis was induced by electrical stimulation of the intimal surface of the left circumflex (LCX) coronary artery. Infusions of PGI2 (25 or 50 ng/kg/min) into the left atrial appendage and aminophylline (20 micrograms/kg/min) or ethylene diamine into the left jugular vein were initiated 10 min before the start of LCX coronary artery stimulation and continued for the 6-hr stimulation period. Every animal in the control (Tris buffer plus ethylene diamine, n = 7), PGI2 (25 ng/kg/min) only (n = 6) and aminophylline only (n = 7) groups developed completely occlusive coronary artery thrombi. In contrast, none of the animals receiving PGI2 (25 ng/kg/min) plus aminophylline or PGI2 (50 ng/kg/min) plus aminophylline underwent occlusive thrombus formation. The average thrombus mass developed in response to intimal injury of the LCX coronary artery was 57 +/- 14 mg (X +/- S.E.M.) in the control group. Aminophylline administration in conjunction with PGI2 infusion at doses of 25 and 50 ng/kg/min significantly reduced thrombus mass to 11 +/- 2 and 10 +/- 1 mg, respectively (P less than .05). PGI2 (25 ng/kg/min) plus aminophylline reduced mean arterial pressure by 12% from 116 +/- 5 to 102 +/- 4 mm Hg. These data demonstrate that the combined administration of aminophylline with low-dose PGI2 provides antithrombotic efficacy while minimizing the detrimental hemodynamic effects of large-dose PGI2 administration.

Aminophylline↗

PubMed1982

The effect of ibuprofen on accumulation of indium-111-labeled platelets and leukocytes in experimental myocardial infarction.

To assess the ability of ibuprofen to influence the extent of platelet aggregation and leukocyte infiltration during acute myocardial infarction, autologous indium-111 (111-In)-labeled platelets or leukocytes were injected before 60 minutes of left circumflex coronary artery (LCx) occlusion, followed by 24 hours of reperfusion in the canine heart. Myocardial infarct size, as a percent of the area at risk, was reduced in the ibuprofen-treated group (12.5 mg/kg i.v. every 4 hours beginning 30 minutes before LCx occlusion) by 40%, from 48 +/- 4% in control animals to 29 +/- 4% in ibuprofen-treated dogs (p = 0.005). Quantification of the platelet-associated 111In radioactivity in irreversibly injured myocardium indicated that ibuprofen did not alter the accumulation of platelets in infarcted myocardium. In contrast, leukocyte accumulation in infarcted tissue was reduced significantly. In tissue samples with 0.41-0.60 gram infarct, the infarcted/normal ratio of leukocyte radioactivity was 12 +/- 2 in control dogs and 4 +/- 1 in ibuprofen-treated dogs, which represents a 67% reduction in leukocyte accumulation in ibuprofen-treated compared with control dogs. Similar reductions were found in other gram-infarct-weight categories. Although both platelets and leukocytes accumulate in infarcted canine myocardium, ibuprofen may exert its beneficial effect on ischemic myocardium by suppressing the inflammatory response associated with myocardial ischemia and infarction.

Animals↗

PubMedDate not supplied

Effect of zomepirac on experimental coronary artery thrombosis and ischemic myocardial injury in the conscious dog.

The nonsteroidal anti-inflammatory agent, zomepirac, was evaluated for its in vivo antithrombotic effects in conscious canines by inducing left circumflex (LCX) coronary artery thrombosis with low-amperage electrical stimulation (50 muA for 24 h) of the intimal surface of the vessel. Zomepirac, 10 mg/kg i.v., given at 0 and 12 h, prevented occlusive coronary artery thrombosis (seven of 10 controls developed occlusive thrombi, compared to one of eight zomepirac-treated animals; p = 0.02). LCX thrombus mass also was reduced by zomepirac (control: 24.0 +/- 4.0 mg; zomepirac: 10.2 +/- 2.4 mg, p less than 0.05; means +/- SEM). Left ventricular infarct mass due to occlusive LCX coronary artery thrombosis was likewise reduced. In a separate series of experiments, zomepirac (10 mg/kg i.v.), given 30 min before occlusion, failed to limit the extent of irreversible myocardial injury after temporary (90 min) LCX coronary artery occlusion in the canine. Infarct size, as a percent of the area at risk of infarction, averaged 47.8 +/- 3.9% in controls, and 40.4 +/- 7.5% in zomepirac-treated animals (means +/- SEM). No difference in the mass of myocardium at risk of infarction was observed between the two groups. In this latter study, zomepirac produced no significant hemodynamic effects. Ex vivo platelet aggregation in response to collagen and arachidonic acid was decreased significantly by zomepirac, but aggregation to ADP was unaffected. These results suggest that zomepirac possesses anti-thrombotic properties, but lacks intrinsic cardioprotective effects. Therefore, zomepirac may be of potential value in the prevention of coronary artery thrombosis owing to its ability to modify platelet reactivity.

Animals↗

PubMedDate not supplied

Experimental coronary artery thrombosis in the absence of thromboxane A2 synthesis: evidence for alternate pathways for coronary thrombosis.

The actions of the thromboxane synthetase inhibitor, U-63557A, were evaluated in vivo in anesthetized open-chest dogs by inducing left circumflex coronary artery (LCCA) thrombosis with low amperage electrical stimulation (100 microA for 6 h) of the intimal surface of the vessel, and ex vivo by assessing platelet aggregation and TXB2 production. U-63557A, 10 mg/kg + 5 mg/kg/h i.v., reduced ex vivo platelet aggregation in response to arachidonic acid (0.65 mM) by 93 +/- 2% (p less than 0.05, means +/- SEM), whereas the concurrent formation of TXB2 was decreased by 78 +/- 8% (p less than 0.05). TXB2 concentration also was reduced significantly in vivo as measured from coronary sinus blood samples; however, 6-keto-PGF1 alpha concentration was unchanged from predrug values. Despite the significant inhibition of platelet aggregation and TXB2 production, thrombus mass was not reduced: control, 32.0 +/- 5.9 mg (n = 7); U-63557A, 30.8 +/- 12.0 mg (n = 5, p = NS). These results suggest that U-63557A effectively inhibits TXA2 synthetase, but lacks antithrombotic activity in our experimental model. Therefore, substances other than TXA2 may be capable of mediating occlusive coronary artery thrombosis.

6-Ketoprostaglandin F1 alpha↗