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Biomedical subjects

T A Patrick

Publications and source records attributed to T A Patrick.

33 records · Page 2Linked to original sources
PubMed1981

Limitations of postextrasystolic potentiation in identifying ischemic myocardium.

To evaluate the usefulness of postextrasystolic potentiation in differentiating ischemic yet viable myocardium from infarcted myocardium, 20 dogs were chronically instrumented with left ventricular pressure gauges, left circumflex coronary artery flow probes, occluders, pacing wires, and ultrasonic segment-length transducers. Ten dogs had acute (1 h) coronary occlusions followed by reperfusion (4 days) and were then killed. Ten more dogs had more prolonged (1 mo) occlusions and were then killed. Timed premature ventricular contractions were induced, and the postextrasystolic beat was evaluated. In ischemic segments that were hypokinetic, postextrasystolic potentiation of shortening occurred in both groups. In ischemic segments that were akinetic or dyskinetic, potentiation of shortening did not occur in either group. Both groups showed recovery of shortening, and histologically normal myocardium was identified in the region between the segments in all animals. Thus, akinetic and dyskinetic segments did not show postextrasystolic potentiation of shortening, even though the tissue was viable and showed functional recovery. Failure to improve shortening after a premature ventricular beta in an ischemic segment does not necessarily indicate nonviable myocardium.

Action Potentials↗
PubMed1976

Role of arterial baroreceptors in mediating cardiovascular response to exercise.

The role played by the major arterial baroreceptor reflexes in the cardiovascular response to exercise was examined by comparing the responses of untethered conscious dogs instrumented for the measurement of aortic pressure and cardiac output with those of dogs with total arterial barorecptor denervation (TABD). Moderately severe levels of exercise (12 mph) in intact dogs increased cardiac output from 111 +/- 17 ml/kg per min, increased heart rate from 101 +/- 5 to 265 +/- 8 beats/min, and reduced total peripheral resistance from 0.039 +/- 0.003 to 0.015 +/- 0.002 mmHg/ml per min. Dogs with TABD responded in a very similar fashion; exercise increased cardiac output from 119 +/- 8 to 356 /+- 23 ml/kg per min, increased heart rate from 122 +/- 7 to 256 +/- 5 beats/min, and decreased total peripheral resistance from 0.042 +/- 0.005 to +/- 0.015 +/- 0.001 mmHg/ml per min. The reflex heart rate responses to intravenous bolus doses of methoxamine were also examined in intact animals, both at rest and during exercise. Methoxamine caused striking bradycardia at rest, but little bradycardia during exercise. These results suggest that the arterial baroreceptor reflex is normally turned off during severe exercise and thus does not modify significantly the cardiovascular response to exercise.

Animals↗
PubMed1976

Effects of isoproterenol on regional myocardial function, electrogram, and blood flow in conscious dogs with myocardial ischemia.

The effects of coronary occlusion and of subsequent isoproterenol infusion were examined in conscious dogs. Left ventricular (LV) function was assessed by measurements of LV diameter, pressure, velocity and dP/dt/P, and regional myocardial function was assessed by measurements of segment length (SL) and velocity of SL shortening in normal, border, and ischemic zones. Regional myocardial function was measured from the same sites, along with intramyocardial electrograms and regional myocardial blood flow as determined by radioactive microspheres. Coronary occlusion resulted in graded loss of function from the normal to severely ischemic zones with graded flow reductions and graded increases in ST segment elevation. Isoproterenol improved overall LV function, and function in the normal zone. Isoproterenol also improved function in 19 of 21 border-zone segments and in all moderately ischemic segments, while elevating further the ST segments. These changes were accompanied by increases in myocardial blood flow. In contrast, in severely ischemic segments, isoproterenol resulted in a deterioration of function, in that paradoxical motion occurred in segments previously akinetic during systole, while paradoxical motion was intensified in those segments in which it was already present. These changes were accompanied by further ST segment elevation but not by concurrent increases in blood flow. In addition, in 2 of 21 border zone segments, myocardial blood flow fell and these segments responded to isoproterenol with complete loss of function; paradoxical motion developed. Thus, in the conscious dog, a strong inotropic agent can improve function, even in the ischemic myocardium, as long as the required additional blood flow can be provided wither through primary or collateral channels.

Animals↗
PubMed1974

Effects of catecholamines, exercise, and nitroglycerin on the normal and ischemic myocardium in conscious dogs.

The effects of isoproterenol, norepinephrine, dobutamine, exercise, and nitroglycerin on left ventricular diameter, pressure, velocity of shortening, dP/dt, dP/dt/P, arterial pressure, left circumflex coronary blood flow, and coronary vascular resistance were examined in healthy conscious dogs with normal coronary perfusion and in the same animals after moderate global ischemia had been induced by partial occlusion of the left main coronary artery. In the normal nonischemic heart, all interventions improved left ventricular performance, as evidenced by increases in dP/dt/P and velocity at the same or lower left ventricular end-diastolic diameter. Interventions, which in the normal heart caused large increases in heart rate and myocardial contractility, e.g. isoproterenol and exercise, or which decreased coronary perfusion pressure, e.g. nitroglycerin or isoproterenol, elicited paradoxical responses in moderate global ischemia, i.e., left ventricular enddiastolic diameter and pressure rose, and dP/dt/P and velocity fell substantially. On the other hand, norepinephrine, which increased coronary perfusion pressure along with myocardial contractility but did not increase heart rate, improved left ventricular function. Dobutamine, which did not alter heart rate or arterial pressure substantially while improving myocardial contractility, produced an intermediate response between that of norepinephrine and isoproterenol in the presence of moderate global myocardial ischemia. Thus, interventions that increase myocardial O(2) requirements, by increasing heart rate and myocardial contractility without augmenting coronary perfusion pressure, can produce a paradoxical depression of ventricular function in the presence of global myocardial ischemia.

Adrenergic beta-Agonists↗
PubMedDate not supplied

Single-chain Fv/folate conjugates mediate efficient lysis of folate-receptor-positive tumor cells.

Bispecific antibodies that bind to a tumor antigen and the T cell receptor (TCR) redirect cytotoxic T lymphocytes (CTL) to lyse tumor cells which have escaped normal immune recognition mechanisms. One well-characterized tumor antigen, the folate receptor (FR), is expressed on most ovarian carcinomas and some types of brain cancer. Recently, it was shown that conjugates of folate and anti-TCR antibodies are extremely potent bispecific agents that target tumor cells expressing the high-affinity folate receptor, but not normal cells expressing only the reduced folate carrier protein. In this paper, it is shown that the size of these conjugates can be reduced to the smallest bispecific agent yet described (30 kDa) by attaching folate to a single-chain antibody, scFv, of the anti-TCR antibody KJ16. The scFv/folate conjugates are as effective as IgG/folate conjugates in mediating lysis of FR4 tumor cells by CTL. The optimal folate density was in the range of 5-15 folate molecules per scFv or IgG molecule, which yielded half-maximal lysis values (EC50) of approximately 40 pM (1.2 ng/mL for scFv). Finally, the scFv/folate conjugates could efficiently target tumor cells even in the presence of free folic acid at concentrations that are normally found in serum. Compared to conventional bispecific antibodies, the small size of scFv/folate conjugates may prove advantageous in the ability to penetrate tumors and in reduced immunogenicity.

Animals↗
PubMedDate not supplied

A regional ultrasonic technique to measure left ventricular performance during coronary artery bypass.

Miniaturized, highly accurate pressure transducers and segment length measuring devices have been proven a safe, practical and stable method of analyzing cardiac performance in both acute and chronic animal experimentation. We have utilized a micromanometer-tipped intraventricular catheter and an ultrasonic segment length gauge implanted in the subendocardial layer of the left ventricle at the time of cardiac surgery to measure changes in systolic function and diastolic compliance prior to and after the completion of the operative procedure in man. No complications of this technique were encountered in the thirty patients studied. Continuous improvements in instrument design, data collection and data processing suggest future clinical applications are possible and desirable.

Compliance↗