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Biomedical subjects

J T Flaherty

Publications and source records attributed to J T Flaherty.

At least 73 records · Page 4Linked to original sources
PubMed1982

Optimal myocardial protection with fluosol cardioplegia.

An oxygenated perfluorocarbon cardioplegic solution was examined, utilizing a blood-perfused canine model. Twenty-one animals were divided into three equal groups, and each animal received Fluosol cardioplegia at one of three infusion temperatures: 20 degrees C, or 4 degrees C. All hearts underwent 90 minutes of ischemia, during which time 150 ml of the cardioplegic solution was infused every 30 minutes. Myocardial oxygen and carbon dioxide tensions (PmO2 and PmCO2) were monitored continually using mass spectrometry, and myocardial oxygen consumption was calculated with each cardioplegic injection. The mean increase in PmO2 was 7.1 +/- 0.9 mm Hg with 20 degrees C Fluosol infusions, 31.1 +/- 4.7 mm Hg with 10 degrees C Fluosol injections, and 22.2 +/- 4.7 mm Hg with infusions of 4 degrees C Fluosol. Average myocardial oxygen consumptioN, expressed as cubic centimeters of oxygen per 100 gm of left ventricle (wet weight), was 21.2 +/- 0.5 with 20 degrees C Fluosol, 22.8 +/- 1.3 for 10 degrees C Fluosol, and 19.6 +/- 1.0 for 4 degrees C Fluosol. Mean myocardial temperatures with infusions of 20 degrees C, 10 degrees C, and 4 degrees C solutions were 21.4 +/- 0.1 degree C, 16.9 +/- 0.4 degree C, and 15.9 +/- 0.5 degree C, respectively. After 45 minutes of reperfusion, maximum rate of rise of left ventricular pressure, expressed as percentage of preischemic control, was 70.9 +/- 3.9% for 20 degrees C Fluosol, 90.9 +/- 3.2% for 10 degrees C Fluosol, and 90.4 +/- 2.3% for 4 degrees C Fluosol (p less than 0.005, 20 degrees C versus 10 degrees C, 4 degrees C Fluosol). In addition, the 10 degrees C and 4 degrees C Fluosol hearts had essentially normal structure by light and electron microscopy. These data demonstrate tht Fluosol cardioplegia results in near optimal myocardial protection when infused at cold temperatures (4 degrees C to 10 degree C). The increases intramyocardial oxygen and myocardial oxygen consumption with each injection demonstrate that there is enhanced oxygen delivery and utilization, which may account for the improved functional recovery observed in these hearts.

Animals↗
PubMed1982

Mechanisms of ischemic myocardial cell damage assessed by phosphorus-31 nuclear magnetic resonance.

Phosphorus-31 nuclear magnetic resonance (31P NMR) can estimate tissue intracellular pH as well as the content of high-energy phosphate metabolites in isolated perfused hearts. We used 31P NMR to examine mechanisms associated with the recovery of ventricular function in hearts subjected to global ischemia and reperfusion, with special emphasis on intracellular pH, a previously unreported variable. Single-dose and multiple-dose administration of a hyperkalemic cardioplegic solution were compared with hypothermia alone in 18 isolated perfused rabbit hearts. Hearts in group 1 were subjected to 24 degrees C hypothermia during 60 minutes of global ischemia; group 2 hearts received a single injection of 37-mM KCL cardioplegic solution at 10 degrees C at the onset of ischemia; and group 3 hearts received a similar initial cardioplegic injection followed by two subsequent 24 degrees C injections at 20-minute intervals during the ischemic period. Using an intraventricular balloon, maximal dP/dt provided a quantitative index of left ventricular performance before and after ischemia. Return of ventricular function expressed as a percentage of control was 54 +/- 11% for group 1, 84 +/- 6% for group 2, and 101 +/- 18% for group 3. Differences in the rate of development of intracellular acidosis were noted during the 60-minute ischemic period. Intracellular pH fell to 6.09 +/- 0.12 in group 1, 6.31 +/- 0.09 in group 2, an 6.79 +/- 0.03 in group 3. In all three groups intracellular pH returned to control (pH 7.20) within 10 minutes of reflow. The metabolic correlates of functional recovery appeared to be the tissue content of ATP at the end of ischemia and after reflow. ATP content at the end of ischemia was 22 +/- 2% of control in group 1 hearts, 31 +/- 4% in group 2 and 64 +/- 2% in group 3. After 45 minutes of reperfusion, ATP levels recovered to 33 +/- 9% of control in group 1, to 71 +/- 9% in group 2 and to 86 +/- 6% in group 3. Although there were no differences between groups in the content of creatine phosphate after 60 minutes of ischemia, the rates of creatine phosphate decline were dissimilar. Further, during the early reflow period, a marked overshoot in tissue creatine phosphate was detected, especially in groups 1 and 2. Histologic damage assessed by light microscopy correlated with the metabolic data, confirming that multidose cardioplegia provided the best preservation of cellular morphology. These results demonstrate that the magnitude of intracellular acidosis and the associated increase in inorganic phosphate correlate inversely with recovery of postischemic ventricular structure and function. ATP, but not creatine phosphate, content correlates with return of contractile performance after reperfusion. The overshoot in creatine phosphate during early reperfusion might impede optimal restoration of ATP content and, as a result, optimal recovery of cell functions.

Adenosine Triphosphate↗
PubMed1982

Comparison of intravenous nitroglycerin and sodium nitroprusside for treatment of acute hypertension developing after coronary artery bypass surgery.

The present study was designed to test the hypothesis that i.v. nitroglycerin is as effective as sodium nitroprusside for managing acute hypertension early after coronary artery bypass surgery. Seventeen patients received both nitroglycerin and nitroprusside in a randomized crossover protocol. Infusion rates were increased stepwise to lower mean arterial pressures comparably with each drug. In 14 of 17 patients, similar infusion rates of the two vasodilators resulted in equal lowering of both blood pressure and systemic vascular resistance. In the remaining three patients, very high infusion rates of nitroglycerin were required and achieved only 20-50% of nitroprusside's response in two of three. Hemodynamic responses to the two vasodilators were similar, except that nitroglycerin increased cardiac output more than nitroprusside did. In contrast, pulmonary gas exchange responses differed in that nitroglycerin improved intrapulmonary shunting, while nitroprusside worsened it. Similarly, nitroglycerin resulted in a significantly smaller increase in the alveolar arterial oxygen gradient than did nitroprusside. These results suggest that in the majority of patients, i.v. nitroglycerin was as effective as nitroprusside in controlling acute hypertension after coronary artery bypass surgery. In addition, nitroglycerin appeared to have more favorable effects on pulmonary gas exchange. Because nitroglycerin has more beneficial effects on intercoronary collateral blood flow in the setting of regional ischemia, it may be preferable to nitroprusside in patients with ischemic heart disease.

Blood Pressure↗
PubMed1982

Therapeutic scope of intravenous nitroglycerin.

Sublingual nitroglycerin has been the time-honored therapy for angina pectoris for nearly a century. Sustained-action oral forms and cutaneous ointment have been used for perhaps ten years for prophylactic treatment of angina and even more recently have been recommended for use in congestive failure. For the past six years investigators at Johns Hopkins Hospital have been administering intravenous nitroglycerin to patients with acute myocardial infarction with and without left ventricular failure. More recently, we have employed intravenous nitroglycerin to manage acute hypertension developing in patients before and after coronary artery bypass graft surgery. I would like to review with you the current indications for intravenous nitroglycerin and the beneficial effects that would be expected in each clinical situation. I will draw on our own clinical experience obtained in nearly 200 patients and, when necessary, on the recent medical literature.

Acute Disease↗
PubMed1982

Failure of blood cardioplegia to protect myocardium at lower temperatures.

To assess the effect of temperature, oxygenated blood and crystalloid cardioplegic solutions (CPs) at infusion temperatures of 20 degrees C, 10 degrees C and 4 degrees C were compared. The amount of potassium in each CP was 25 mEq/l. There were six study groups with seven canine hearts in each group, all of which were subjected to 90 minutes of global ischemia at 20 degrees C, 10 degrees C or 4 degrees C, followed by 45 minutes of normothermic reperfusion. During ischemia, either blood or crystalloid CP was given every 30 minutes. With each infusion, any change in myocardial oxygen tension was recorded using mass spectrometry, and oxygen consumption (MVO2) was calculated. Left ventricular (LV) function was assessed before and after ischemia in all hearts by measuring isovolumic developed pressure using an intraventricular balloon. Injection of 20 degrees C blood CP resulted in a mean increase in intramyocardial oxygen tension (PO2) of 7 mm Hg. At 10 degrees C or 4 degrees C, blood CP infusions did not cause a significant increase in intramyocardial PO2, while with crystalloid CP, intramyocardial PO2 did not increase at any of the three infusion temperatures. The mean MVO2 with each blood CP injection, expressed as ml O2/100 g LV wet weight, was 16.5 +/- 0.8 for 20 degrees C blood, 4.1 +/- 0.3 for 10 degrees C blood and 3.5 +/- 0.4 for 4 degrees C blood (p less than 0.001, 20 degrees C blood vs 10 degrees C and 4 degrees C blood). MVO2 with each crystalloid CP injection was 0.9 +/- 0.1 for 20 degrees C CP, 0.8 +/- 0.1 for 10 degrees C CP, and 0.7 +/- 0.1 for 4 degrees C CP. Recovery of developed pressure after 45 minutes of reperfusion, expressed as a percentage of preischemic control, was 76.0 +/- 3.4% or 20 degrees C blood CP, 65.6 +/- 2.3% for 10 degrees C blood CP, and 54.0 +/- 2.7% for 4 degrees C blood CP (p less than 0.05, 20 degrees C blood CP vs 10 degrees C and 4 degrees C blood CP). Recovery of developed pressure, also expressed as a percentage of preischemic control, was 56.6 +/- 1.4% for 20 degrees C crystalloid CP, 72.9 +/- 3.0% for 10 degrees C crystalloid CP, and 72.0 +/- 2.3% for 4 degrees C crystalloid CP (p less than 0.05, 20 degrees C crystalloid CP vs 10 degrees C and 4 degrees C crystalloid CP). These data show that blood CP is most effective when infused at 20 degrees C. The use of 10 degrees C blood CP enhanced myocardial cooling, but was of no additional benefit, presumably because there was little oxygen delivery. Blood CP at 4 degrees C resulted in significantly poorer preservation of LV function. Crystalloid CP infused at either 4 degrees C or 10 degrees C was as effective as 20 degrees C blood CP, despite the absence of oxygen use by hearts treated with crystalloid CP.

Animals↗
PubMed1982

Assessment of myocardial protection during global ischemia with myocardial gas tension monitoring.

Intramyocardial gas tension monitoring with mass spectrometry allows for the continuous assessment of myocardial metabolic activity during prolonged global ischemia. With aortic cross-clamping there is a rapid decrease in intramyocardial oxygen tension (PmO2) and a steady increase in carbon dioxide tension (PmCO2). In laboratory studies the extent to which myocardial metabolic activity is reduced has correlated with the degree of myocardial protection being afforded. In the present study the metabolic consequences of single-dose versus multiple-dose infusions of a hyperkalemic cardioplegic solution were compared in 23 patients undergoing aortic valve replacement (AVR) for severe aortic stenosis. Group I (n = 13) had single-dose cardioplegia during AVR, while group II (n = 10) had multiple-dose cardioplegia. The preoperative status and the surgical procedures were identical except for two multiple-dose patients who also underwent single coronary bypass grafting. In group I the PmCO2 rose steadily and at cross-clamp release was 182 +/- 20 mm Hg, while in group II the PmCO2 rose only to 77 +/- 8 mm Hg (P less than 0.01). During reperfusion the peak PmCO2 in group I was 219 +/- 22 mm Hg versus 111 +/- 5 mm Hg in group II (P less than 0.01). After operation six patients in group I required pharmacologic support, and two other patients died of low cardiac output. In contrast, only one patient in group II required inotropic support, and there were no deaths. The significantly lower PmCO2 values with multiple-dose cardioplegia suggest both reduced metabolic activity and washout of metabolic end products, with resultant improved myocardial protection, evidenced by less postoperative left ventricular dysfunction.

Adult↗
PubMed1981

The harmful effects of ventricular distention during postischemic reperfusion.

To assess the effects of left ventricular distention during the early reperfusion period following ischemic arrest, 16 canine heart preparations were subjected to 45 minutes of hypothermic (27 degree C) cardioplegic arrest and normothermic reperfusion. Isovolumic left ventricular developed pressure and rate of rise of left ventricular pressure (dp/dt) were measured with an intraventricular balloon; endocardial/epicardial flow ratios were determined with microspheres; and myocardial gas tensions were monitored with mass spectrometry. During early reperfusion, Group 1 hearts (n = 8) were not distended (end-diastolic pressure = 0). Group 2 hearts (n = 8) were subjected to an enddiastolic pressure of 20 mm Hg for the initial 15 minutes of reperfusion. Group 2 hearts demonstrated impaired subendocardial blood flow after 5 minutes of reflow (0.75 +/- 0.06 vs 0.96 +/- 0.04, endocardial/epicardial flow rates, Group 2 vs Group 1) and persistent elevation of intramyocardial carbon dioxide (CO2) tension (68 +/- 4 vs 51 +/- 4 mm Hg, Group 2 vs Group 1). In addition, postischemic ventricular function was significantly worse in Group 2 hearts (60 +/- 7 vs 79 +/- 3% of control dP/dt, Group 2 vs Group 1, and 53 +/- 6 vs 81 +/- 5% of control left ventricular developed pressure, Group 2 vs Group 1). These data demonstrate that even mild distention during early reperfusion can result in reduced subendocardial perfusion and delayed washout of tissue CO2. Although myocardial blood flow and CO2 tension subsequently returned to normal in the distended hearts, left ventricular performance remained significantly depressed. This injury can occur clinically in nonvented hearts prior to the resumption of effective ventricular contraction.

Animals↗
PubMed1981

Mechanism of elevated left ventricular end-diastolic pressure after ischemic arrest and reperfusion.

The effects of ischemic arrest and reperfusion on isovolumic end-diastolic pressure, diastolic pressure-volume curves, and indices of ventricular relaxation and contractility were studied in an isolated feline heart preparation. In hearts subjected to 60 min of normothermic (37 degrees C) ischemic arrest, isovolumic developed pressure, and dP/dtmax during reperfusion returned to only approximately 60% of prearrest control levels. Isovolumic end-diastolic pressure (Ped) increased 37.0 +/- 4.3 mmHg and the time constant of ventricular relaxation was prolonged. Hearts maintained at 27 degrees C hypothermia during the 60-min ischemic period demonstrated improved contractile performance (approximately 100% of control), less elevation of Ped (21.4 +/- 4.5 mmHg), and no significant increase in the time constant of relaxation. In both groups of hearts, postarrest end-diastolic pressure-volume curves were shifted up and to the left, whereas indices of ventricular stiffness and muscle stiffness remained unchanged. These data suggest that the rise in isovolumic end-diastolic pressure observed after 1 h of ischemic arrest and reperfusion is the result of an upward and to the left shift of the entire diastolic pressure-volume relationship of the left ventricle. This shift does not appear to be related to diminished contractile performance or incomplete relaxation. Furthermore, the shift is not due to a change in muscle compliance, but to a reduction in the unstressed volume of the ventricle, which most likely results from myocardial contracture and edema.

Animals↗
PubMed1981

Effects of nitroglycerin on regional myocardial ischemia induced by atrial pacing in dogs.

The exact mechanism or mechanisms by which nitroglycerin exerts its beneficial effect on pacing-induced regional myocardial ischemia has not been ellucidated previously. In an open-chest, anesthetized canine preparation a fixed, flow limiting stenosis was applied to the left anterior descending (LAD) coronary artery and heart rate was increased by atrial pacing. Mass spectrometry was used to measure myocardial oxygen (PmO2) and carbon dioxide (PmCO2) tensions. Myocardial blood flow was measured by the radioactive microsphere technique. Application of the stenosis resulted in regional decreases in PmO2 and increases in PmCO2 of greater magnitude in the subendocardial than in the subepicardial layer. Atrial pacing resulted in a further decrease in PmO2 and increase in PmCO2 as well as a reduction in subendocardial blood flow. Nitroglycerin (TNG) infusion reduced mean arterial pressure 20 mm Hg, resulting in a 14 mm Hg reduction in PmCO2 in the more ischemic subendocardial layer (P less than 0.05). Myocardial blood flow decreased in all regions; however, the magnitude of this decrease was less in the ischemic region. Addition of aortic constriction abolished both the afterload and preload lowering effects of nitroglycerin but improved ischemic zone blood flow. These data demonstrate that nitroglycerin reduces the severity of pacing-induced regional myocardial ischemia primarily by reducing the determinants of myocardial oxygen demand. We found that when these effects are counteracted, improvement in myocardial oxygen supply becomes the dominant mechanism.

Animals↗
PubMed1981

Combined administration of nitroglycerin and propranolol to patients with acute myocardial infarction.

Hemodynamic effects of combined nitroglycerin and propranolol administration were investigated in patients with acute myocardial infarction. After nitroglycerin infusion decreased the mean arterial pressure by 20 mm Hg for one hour, nitroglycerin was continued, and patients were given 0.033 mg/kg of propranolol every five minutes for a total dose of 0.1 mg/kg, or until there was a decrease in heart rate to less than 60 beats/min, an increase in left ventricular filling pressure (LVFP) to greater than 15 mm Hg, or a decrease in systolic arterial pressure to less than 85 mm Hg. Seven of eight patients with initial LVFP less than or equal to 15 mm Hg and three of seven with initial LVFP greater than 15 mm Hg received 0.1 mg/kg of propranolol. Propranolol significantly decreased heart rate. Although pressure time/minute decreased significantly, the magnitude of its decrease was small, suggesting only a minimal effect on myocardial oxygen demands. The LVFP increased after giving propranolol but remained less than the control value. Simultaneous administration of nitroglycerin likely prevented further increases, since LVFP increased after cessation of nitroglycerin infusion, and three patients subsequently had pulmonary edema. Propranolol administration resulted in a significant increase in peripheral vascular resistance and a decrease in cardiac output.

Blood Pressure↗
PubMed1981

Superiority of perfluorocarbon cardioplegia over blood or crystalloid cardioplegia.

Oxygenated Fluosol-43 cardioplegia (CP), a perfluorocarbon with high oxygen solubility, was compared with crystalloid and oxygenated blood cardioplegia. Potassium in each CP was 25 mEq/l. Thirty perfused rabbit hearts in three groups of 10 hearts each underwent 100 minutes of global ischemia at 20 degrees C, followed by 45 minutes of reperfusion at 37 degrees C. During ischemia, CP was given every 20 minutes. With each CP injection, increases in myocardial oxygen tension were recorded using mass spectrometry and oxygen consumption (MVO2) was calculated. Left ventricular function was assessed before and after ischemia by measuring isovolumic developed pressure and dP/dt with an intraventricular balloon. Intramyocardial PO2 increased by 19.6 +/- 1.8 mm Hg in the Fluosol CP group, 0.4 +/- 0.1 mm Hg in the crystalloid CP group and 1.5 +/- 0.3 mm Hg in the blood CP group (p less than 0.001, Fluosol CP vs crystalloid CP and blood CP). MVO2 with each CP injection, expressed as ml O2/100 g dry weight, was 203.8 +/- 7.0 for Fluosol CP, 20.4 +/- 1.2 for crystalloid CP and 39.2 +/- 4.3 for blood CP (p less than 0.001 Fluosol CP vs crystalloid CP and blood CP). Recovery of maximal dP/dt after 45 minutes of reperfusion, expressed as a percentage of preischemic control, was 75.6 +/- 4.0% for Fluosol CP, 60.9 +/- 5.5% for crystalloid CP and 53.4 +/- 3.7% for blood CP (p less than 0.02 Fluosol CP vs blood CP and crystalloid CP). These data clearly show that the use of Fluosol cardioplegic solution enhanced oxygen delivery and use compared with blood and crystalloid cardioplegic solutions. The marked increase in intramyocardial oxygen and MVO2 with each injection of Fluosol CP shows that there is effective aerobic metabolic activity during ischemia, which may explain the improved functional recovery. The failure of blood CP to afford similar protection can be explained by a decreased oxygen release from hemoglobin due to the leftward shift of the oxygen-hemoglobin dissociation curve with hypothermia.

Animals↗
PubMed1981

Beneficial effects of adding propranolol to multidose potassium cardioplegia.

The use of propranolol with multidose potassium cardioplegia was studied in 32 in situ canine hearts subjected to 90 minutes of global ischemia at 15 degrees C and 60 minutes of reperfusion at 37 degrees C. All hearts received potassium (37 mEq/l) every 30 minutes during ischemia. There were four groups of equal size: group 1 received no propranolol, group 2 received low-dose propranolol and group 3 received high-dose propranolol. Group 4 received high-dose propranolol only with the initial potassium infusion. Myocardial CO2 (PmCO2) was monitored by mass spectrometry as an indicator of metabolic activity. An intraventricular balloon was used to measure isovolumic developed pressure, maximal dP/dt and end-diastolic pressure (EDP) before and after ischemia. During ischemia, peak PmCO2 was significantly higher in group 1 (45.6 +/- 2.8 mm Hg) than in groups 2, 3 and 4 (35.2 +/- 2.8 mm Hg, 33.4 +/- 2.8 mm Hg and 30.4 +/0 2.8 mm Hg, respectively) (p less than 0.05). There were no differences between the four groups in systolic ventricular function assessed by developed pressure and dP/dt. Hearts that received high-dose propranolol had significantly lower EDP after 60 minutes of reperfusion (group 3 13.3 +/- 1.5 mm Hg, group 4 10.4 +/0 1.5 mm Hg) compared with group 1 hearts (25.3 +/- 3.8 mm Hg, p less than 0.05). Hearts in groups 3 and 4 exhibited less ischemic injury as assessed by electron microscopy than hearts in groups 1 and 2. These data show that propranolol added to multidose potassium cardioplegia reduced metabolic activity during ischemia and improved ventricular compliance during reperfusion without depressing systolic function. Because left ventricular compliance and morphologic preservation were similar in groups 3 and 4, it appears that a single high dose of propranolol is sufficient and that subsequent doses do not further enhance the beneficial effects.

Animals↗
PubMed1980

Evidence for a flow-independent contribution to the phenomenon of thallium redistribution.

Although thallium-201 is known to redistribute slowly into regions of ischemic myocardium after restoration of blood flow, it is not clear to what extent normalization of flow is an essential requirement for the redistribution process. In a search for a flow-independent component of thallium redistribution, 12 dogs with stenosis of the circumflex coronary artery underwent atrial pacing for either 20 minutes (group I, 6 dogs) or 2 hours (group II, 6 dogs). Radioactive thallium and radioactive microspheres, 7 to 10 mu, were injected after 10 minutes of atrial pacing in both groups. Pacing resulted in a 40 percent reduction in subendocardial blood flow to the circumflex-perfused myocardium in both groups I and II. This relative reduction in flow was maintained at a stable level over the 2 hour pacing period in group II. Thallium activity in the relatively ischemic zone was significantly greater in dogs with 2 hours of pacing (group II) than in those with 10 minutes of pacing (group I). Redistribution of thallium occurred despite the continued presence of reduced flow in circumflex-perfused endocardial tissue. These data suggest that a significant component of thallium redistribution may be flow-independent.

Animals↗
PubMed1980

Effect of multiple-dose potassium cardioplegia on myocardial ischemia, return of ventricular function, and ultrastructural preservation.

To evaluate the myocardial protection afforded by multiple-dose versus single-dose administration of potassium cardioplegic solution, we studied 24 isolated feline hearts before, during, and after 1 hour of ischemic arrest. Intramyocardial gas tensions, ventricular function, histologic preservation, and postischemic myocardial edema were compared in hearts maintained at 27 degrees C during the ischemic period. Equal groups of hearts received no infusion of cardioplegic solution, a single dose of potassium solution at the onset of ischemia, or multiple infusions of the cardioplegic solution throughout the arrest period. During ischemia, single-dose cardioplegic administration resulted in less accumulation of myocardial carbon dioxide (Pmco2) than did hypothermia alone, reflecting a reduction in metabolic activity during ischemia. The fact that multiple-dose cardioplegia further reduced Pmco2 accumulation suggests an intermittent washout of metabolic end products. During reperfusion, hearts protected by multidose cardioplegia demonstrated superior preservation of ventricular performance compared to hearts protected by single-dose cardioplegia or hypothermia alone. In addition, multiple infusions of the cardioplegic solution resulted in optimal structural preservation in both light and electron microscope studies.

Animals↗