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Biomedical subjects

W M Daggett

Publications and source records attributed to W M Daggett.

At least 73 records · Page 4Linked to original sources

Reduction of postischemic myocardial dysfunction by substrate repletion during reperfusion.

We studied the effect of selected metabolic substrates on recovery of myocardial function and ATP concentration when added to the reperfusate after normothermic ischemia. The hearts of 30 anesthetized, open-chest mongrel dogs were subjected to 45 min of global ischemia at 37 degrees C followed by 90 min of reperfusion. Left ventricular function curves were generated on right heart bypass before and at 30 min intervals after the ischemic period. ATP concentration was measured before, at the end of, and 90 min after the ischemic period. Experiments were randomized into five groups distinguished by the content of the myocardial reperfusate during the first 10 min of the reperfusion period. Hearts received either unmodified oxygenated pump blood (control; group I), normothermic oxygenated 28 mmol/liter potassium-blood cardioplegic solution (KBC; group II), 25 mmol/liter glutamate in KBC (group III), 250 mumol/liter adenosine with 1 mg erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride (EHNA) and glutamate in KBC (group IV), or 2 mmol/liter ribose and glutamate (group V) in KBC. Hearts reperfused with KBC showed improvement early (group II vs group I; p less than .02) but not late recovery of left ventricular function over control. Glutamate, which replenishes Krebs cycle intermediates lost during ischemia, increased functional recovery (group III vs group II; p less than .002). Ribose, which is important in purine salvage and resynthesis, added to glutamate-KBC further improved functional recovery (group V vs group III; p less than .01). Adenosine, a precursor of ATP, with EHNA, an inhibitor of rapid adenosine catabolism, added to glutamate-KBC depressed early recovery (group IV vs group III; p less than .01); however, recovery improved with time. Both glutamate and ribose with glutamate in KBC improved ATP recovery (groups III and V vs group II; p less than .002). Thus selective substrate repletion during initial reperfusion after severe normothermic ischemia can improve recovery of myocardial function and ATP concentration.

Adenosine↗

Inability of seven-pinhole myocardial tomography to obtain accurate 201Tl kinetic data.

Seven-pinhole myocardial tomography has been reported to enhance the accuracy of thallium-201 (201Tl) studies in detecting patients with coronary artery disease. To determine if this approach can accurately assess regional 201Tl kinetics, 12 dogs with temporary occlusion (mean 15 min) of either the left anterior descending (LAD) (n = 6) or left circumflex (LCX) (n = 6) coronary artery were studied. Thallium-201 was injected and serial 7-pinhole images were acquired during occlusion and following reflow (mean duration 175 min). Time-activity analysis was obtained from normal and ischemic regions of interest in the central pinhole image and the reconstructed tomographic images (TOMO-ROI). Time-activity data from corresponding normal and ischemic regions were also obtained using a circumferential graph program (TOMO-MAX). In addition, regional myocardial 201Tl activity was recorded continuously with a cadmium telluride radiation probe sutured directly to the posterior myocardial wall. Defects in 201Tl distribution with subsequent partial or complete redistribution were present in 11 of 12 central pinhole images and tomographic studies. In the normal and ischemic anterior myocardial segments the percentage change in 201Tl activity in the central pinhole image from occlusion to the end of reflow correlated well with the percentage change in activity for both TOMO-ROI (r = 0.93) and TOMO-MAX (r = 0.85). In the normal posterior segments the percentage change in 201Tl activity in the central pinhole image correlated well with TOMO-ROI (r = 0.98) and TOMO-MAX (r = 0.87).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Electrophysiologic studies before and after myocardial revascularization in patients with life-threatening ventricular arrhythmias.

Electrophysiologic studies with programmed cardiac stimulation were performed in a selected group of 17 patients with severe proximal coronary artery disease involving at least 2 major vessels and left ventricular ejection fractions greater than 30% who were undergoing coronary artery bypass graft surgery after prehospital cardiac arrest or ventricular tachycardia (VT) unassociated with acute myocardial infarction. Before surgery and without antiarrhythmic drug therapy, programmed cardiac stimulation induced ventricular fibrillation (VF) in 4 patients, and VT (greater than or equal to 5 beats) in 11 patients. Inducible VT or VF was suppressed by antiarrhythmic drugs in 7 of 13 patients in whom they were tried. Patients underwent coronary artery bypass graft surgery unassociated with perioperative myocardial infarction. When studied again an average of 19 days after surgery, 10 patients had no inducible VT or VF without antiarrhythmic drug therapy; 6 had induced VT. One patient had spontaneous VT. An effective antiarrhythmic regimen that suppressed inducible or spontaneous VT, or both, was defined by serial electrophysiologic studies in 4 patients, whereas 3 patients continued to manifest electrically inducible VT with all antiarrhythmic regimens tested. All but 1 patient, in whom postoperative VT could not be suppressed, are free of arrhythmias after a mean follow-up period of 23 months (range 6 to 53). It is concluded that myocardial revascularization alone may improve the abnormal electrophysiologic findings in certain patients; however, this effect of coronary artery bypass graft surgery is unpredictable, and pre- and postoperative electrophysiologic studies are recommended as part of the evaluation of these patients.

Aged↗

The efficacy of postoperative autotransfusion in patients undergoing cardiac operations.

The efficacy of postoperative autotransfusion in lowering the requirement for banked-blood transfusion was studied in two groups, each having 168 patients, who underwent cardiac operations between April, 1979, and May, 1980. A Sorenson autotransfusion system was available for use in the autotransfusion group, whereas the control group received routine closed mediastinal drainage. Of the autotransfusion group, 81% met the criterion for autotransfusion (mediastinal losses of 450 ml or more during 4 hours), but only 61% of the autotransfusion group actually received autologous blood (mean autotransfusion volume, 399 +/- 25 ml). The patients receiving autologous blood required significantly less banked blood than their matched controls (447 +/- 60 ml and 744 +/- 83 ml, respectively; p less than 0.001). In the subgroup of patients with large mediastinal losses (more than 1,250 ml), this difference was even greater (autotransfusion, 642 ml compared with control, 1,145 ml; p less than 0.01). Postoperative autotransfusion is a simple, safe, and cost-effective method to reduce dependence on banked blood, especially when mediastinal losses are large. Obtaining maximum benefit requires familiarity of staff with the system and use of a consistent protocol.

Blood Transfusion↗

Global and regional function in the regionally ischaemic left ventricle related to plasma ionised calcium.

To study the response of function in the regionally ischaemic left ventricle to increased and decreased concentrations of plasma ionised calcium, twenty-two anaesthetised dogs were placed on right heart bypass with constant mean aortic pressure and heart rate. Regional (sonomicrometry) and global left ventricular function were assessed before coronary artery ligation. Then, following ligation, function after 45 min stable ionised hypercalcaemia [( Ca2+] = 1.68 +/- 0.01 mmol x litre-1) and hypocalcaemia [( Ca2+] = 0.73 +/- 0.02 mmol x litre-1) were each compared to function during an immediately preceding normocalcaemic period. Control of cardiac output enabled paired comparisons to be made at matched preloads: systolic shortening from common end-diastolic chord lengths (n = 10), and stroke work at common left ventricular end-diastolic pressures (n = 22). With hypercalcaemia, systolic shortening in the ischaemic region (2.11 +/- 0.39 mm preligation) increased from -0.62 +/- 0.17 to -0.04 +/- 0.20 mm (P less than 0.01), whereas in the control region systolic shortening increased from 1.47 +/- 0.12 to 2.00 +/- 0.15 mm (P less than 0.01) reaching its preligation value (1.67 +/- 0.13 mm). Stroke work at a left ventricular end-diastolic pressure of 1.37 kPa increased (0.248 +/- 0.019 to 0.299 +/- 0.021 joules x beat-1, P less than 0.001) but not to preligation levels (0.364 +/- 0.016 joules x beat-1). Hypercalcaemia also increased myocardial oxygen consumption (by 1.0 +/- 0.3 cm3 x min-1 x 100 g-1, P less than 0.005) but not coronary blood flow. With hypocalcaemia, systolic shortening decreased in ischaemic and control regions, global function curves were markedly depressed, and myocardial oxygen consumption did not change but coronary blood flow increased. Thus hypercalcaemia improved function in ischaemic and control regions but improvement in the ischaemic region was small compared with the depression associated with ischaemia itself. Hypercalcaemia also improved global function, but not to preischaemic levels, at an increased oxygen cost.

Animals↗

Coronary reocclusion after selective administration of streptokinase.

Intracoronary streptokinase was given to 40 patients with acute transmural myocardial infarction. In 34 of the patients (85%), it resulted in reflow or improved flow. Six patients showed no reflow and six reocclusion within 2 hours. No consistent explanation was found for this resistance to therapy. Five other patients developed reocclusion after 6 days to 11 months, when heparin or warfarin anticoagulation had been stopped. Percutaneous angioplasty at the time of streptokinase infusion was performed in seven, with six successes. Bypass surgery was performed after successful streptokinase administration in eight. Follow-up revealed recurrent ischemia in patients successfully treated with streptokinase alone, but not in patients with successful angioplasty or bypass surgery. Long-term coronary patency after thrombolysis may require careful anticoagulation or a procedure that modifies or bypasses the residual stenosis.

Angioplasty, Balloon↗

Mechanical valves: a comparative analysis of the Starr-Edwards and Björk-Shiley prostheses.

Despite the requirement of anticoagulation, mechanical valve prostheses offer the advantage of proven durability. We have compared the long-term results of 467 aortic valve replacements and 342 mitral valve replacements using the Starr-Edwards prosthesis with 110 aortic valve replacements and 105 mitral valve replacements using the Björk-Shiley prosthesis from 1973 through 1977. Improvement in New York Heart Association (NYHA) class was noted in greater than 80% of patients in all four groups. Long-term survival with mean follow-up over 5 years was not significantly different between respective groups. The probability of thromboembolic complications, however, was significantly higher (p less than 0.05) with the Starr-Edwards prosthesis in both the aortic and mitral positions. The probability of valve failure, although low for all groups, was significantly higher (p less than 0.05) in the Björk-Shiley mitral group due to late thrombotic occlusion. Use of the Starr-Edwards and Björk-Shiley prostheses is associated with satisfactory functional improvement and similar long-term survival rate. However, the increased risk of valve failure due to late thrombotic occlusion of the Björk-Shiley prosthesis should be considered when choosing a mechanical mitral prosthesis.

Actuarial Analysis↗

Enhanced myocardial protection during ischemic arrest. Oxygenation of a crystalloid cardioplegic solution.

To determine if, during elective cardiac arrest, the myocardial protection afforded by a cold (4 degrees C) crystalloid potassium cardioplegic solution could be improved by oxygenation of the solution, we placed 16 dogs on cardiopulmonary bypass and subjected their hearts to 4 hours of cold cardioplegic arrest. Group 1 hearts (n = 8) received aerated crystalloid solution perfused through the aortic root every 20 minutes. Group 2 hearts (n = 8) were treated identically except that the crystalloid cardioplegic solution was fully oxygenated. Left ventricular function curves (ejecting heart) were generated before arrest (control) and after 45 minutes of reperfusion. A cardiac output of 1,000 ml/min could be attained in only two hearts of Group 1 after reperfusion, whereas all but one heart of Group 2 had excellent functional preservation. Mean postreperfusion adenosine triphosphate (ATP) levels in Group 1 and Group 2 hearts were 62% and 89% of control, respectively (p less than 0.01). Myocardial water content had increased significantly (p less than 0.002) after reperfusion in Group 1, but not in Group 2. During cardioplegic solution infusion, myocardial oxygen consumption (MVO2) was 1.42 +/- 0.15 ml O2/min/100 gm LV for Group 1 and 6.91 +/- 1.27 ml O2/min/100 gm LV for Group 2 (p less than 0.001). Oxygen consumed per minute of arrest was 0.027 +/- 0.003 ml O2/min/100 gm LV for Group 1 and 0.128 +/- 0.015 ml O2/min/100 gm LV for Group 2 (p less than 0.001). Postreperfusion ultrastructural evaluation of two of the Group 1 hearts revealed severe ischemic damage in contrast to the normal ultrastructural appearance of two of the Group 2 hearts. With careful attention given to maintenance of myocardial hypothermia and cardioplegic delivery methods, the myocardial protection afforded by an oxygenated crystalloid cardioplegic solution exceeds that provided by the aerated control and compares favorably with other methods of myocardial protection during ischemic arrest.

Adenine Nucleotides↗

Hypothermic ischemic arrest versus hypothermic potassium cardioplegia in human beings.

To determine if the addition of potassium enhances the myocardial protective effect of intracoronary perfusion hypothermia during aortic cross-clamping, 50 patients undergoing aortocoronary bypass grafting were studied in a randomized, prospective, double-blind fashion. Twenty-six patients received a cold crystalloid solution infused with a handheld syringe into the root of the cross-clamped aorta every 20 minutes, and 24 patients received the same solution but with 25 mEq/L of potassium chloride added, infused in a similar manner. Both groups were analyzed by mortality, rate of perioperative myocardial infarction (electrocardiographic changes, MB-CPK enzyme release, and preoperative and postoperative gated cardiac blood pool scans), intraoperative hemodynamic changes, intraoperative lactate determinations, postoperative arrhythmias, and requirement for pressor or intraaortic balloon pump support. One patient in the potassium cardioplegia group died (massive pulmonary embolism), and none in the hypothermic perfusion group died. Possible perioperative myocardial infarction was diagnosed by more than one marker in 4 of 26 patients in the hypothermic perfusion group and 5 of 24 patients in the potassium group (p = 0.61). There were no differences between the two groups in terms of hemodynamic changes, lactate production, postoperative arrhythmias, or the need for postoperative hemodynamic support. This study in human beings could not demonstrate a specific protective effect of potassium, beyond that afforded by myocardial perfusion hypothermia and wash-out. The data suggest that myocardial hypothermia, achieved through cold intracoronary arterial perfusion, may be the most important beneficial component of so-called cardioplegia for attaining effective intraoperative myocardial preservation in human beings.

Arrhythmias, Cardiac↗

Improved results of surgical management of postinfarction ventricular septal rupture.

Fifty-five patients had surgical repair of postinfarction ventricular septal rupture in Massachusetts General Hospital from 1968 through 1981. In patients operated more than three weeks after infarction, hospital survival has been 93% (14/15). Before 1975 in patients operated less than three weeks after infarction, hospital survival was 41% (7/17). In this same era patents operated for septal rupture with cardiogenic shock present before operation had a hospital survival rate of only 27% (3/11). Before 1975 patients with cardiogenic shock were supported with intra-aortic balloon pumping (IABP) and vasopressors, and operation deferred pending hemodynamic stabilization. Before 1975 patients with anterior septal rupture had a hospital survival rate of 64% (9/14), while patients with posterior septal rupture had a hospital survival rate of only 38% (5/13). This difference in survival according to the location of septal rupture occurred despite comparable numbers of patients in each group requiring early operation, as well as incidence of cardiogenic shock. Since January 1, 1975 patients operated less than three weeks after infarction have had an overall hospital survival rate of 70% (16/23). Of the 10 most recent patients operated early, nine are survivors. In patients with anterior defects 85% (11/13) survived, while in patients with posterior defects 67% survived (10/15). In patients operated with cardiogenic shock present before operation, survival has been 67% (10/15). Changes in management leading to improved results include (1) immediate operation for patients with cardiogenic shock, (2) cold cardioplegic protection of the myocardium, and (3) prosthetic replacement of posterior left ventricular free wall defect, after infarctectomy and septal repair, in patients with posterior septal rupture.

Adult↗

Regional myocardial radiotracer kinetics in dogs using miniature radiation detectors.

An implantable device for continuous measurement of regional myocardial radioisotope activity was designed and validated. The probe consists of a 2-mm3 cadmium telluride crystal surrounded by lead foil housed in a 4.5-mm outer diameter steel cylinder. Activity in serial dilutions of thallium-201 measured by this miniature gamma detector correlated well with activity measured in the well counter (r = 0.99). In vivo probe measurements of regional myocardial thallium-201 activity in a canine model were compared with activity in punch biopsies, again with excellent correlation (r = 0.90). The crystal was mounted on a modified arterial clamp, which was inserted into the left ventricle through, the apex and situated on the endocardial surface of the anterior or posterior wall. It was thus possible to measure regional isotope activity without excessive background from the blood pool and opposite heart wall. The probe was found best suited for monitoring activities of isotopes with energies between 60 and 250 keV. With a pair of these devices, dynamic studies of the myocardial kinetics of radioisotopes such as thallium-201 in normal and ischemic myocardium are now possible.

Animals↗

Isolated coronary artery bypass grafting in patients seventy years of age and older: early and late results.

Increasing longevity makes the consideration of coronary bypass common in elderly patients. Seventy-five patients 70 years of age or older undergoing coronary artery bypass grafting (CABG) for angina pectoris were compared to a control group of 75 patients under 70 years of age. The groups were matched for male:female ratio (46:29), previous infarction (28/75), unstable angina (27/75), and the requirement for preoperative intra-aortic balloon pumping (7/75). Patients under 70 years of age had an average preoperative New York Heart Association (NYHA) class of 3.0 +/- 0.6 (SEM) and an average left ventricular end-diastolic pressure of 15.5 +/- 0.8 mm Hg, compared to 3.3 +/- 0.6 and 12.9 +/- 1.1 mm Hg, respectively, for the older group. Average grafts per patient were 2.7 +/- 0.8 in the younger group and 2.8 +/- 0.1 in the older group. Overall operative mortality for patients under 70 was 4% (3/75) versus 12% (9/75) (p = 0.06) for patients 70 and older. The incidence of chronic stable angina was 2% (1/48) versus 6% (3/48) (p = 0.30). Perioperative infarctions occurred in 7% of those under 70 and 5% of those 70 or older (p = 0.54). Those under 70 averaged 13.8 +/- 0.6 postoperative hospital days versus 18.4 +/- 1.2 hospital days for the older group (p less than 0.05). Follow-up ranged from 2 to 94 months, averaging 22 months for patients under 70 and 24 months for those 70 or older. Late cardiac mortality rates were 4% (3/70) in the younger patients and 3% (2/66) in the older patients (p = 0.53). Current NYHA class was 1.3 +/- 0.7 for those under 70, with 9% reporting angina, and 1.4 +/- 0.7 for those who were 70 or older, with 6% reporting angina. CABG can be performed with acceptable risk in older patients and leads to encouraging symptomatic improvement and late survival.

Aged↗

Comparison of myocardial preservation with hypothermic potassium and nifedipine arrest.

Preservation of regional myocardial function, high-energy phosphate stores and ultrastructure were assessed in 28 canine hearts subjected to 2 hours of global ischemia at either 12 degrees C or 21 degrees C. The preservation achieved with a potassium arrest solution was simultaneously compared in the same heart with either a nifedipine arrest solution or a potassium plus nifedipine arrest solution. There were no statistically significant differences in regional function recovery between the three arrest solutions at either temperature. At 12 degrees C, slightly better functional preservation was noted for each solution. End-systolic chord length was significantly less elongated after preservation at the lower temperature (p = 0.03). The concentration of ATP and myocardial water content were not significantly better preserved with any solution at either temperature. Myocardial ultrastructure was well preserved regardless of the solution or temperature used. The degree of hypothermia appears to be more important to functional preservation than differences between the three solutions tested. We conclude that with respect to preservation of myocardial function, high-energy phosphate stores, water content and ultrastructure, nifedipine arrest offers no advantages over potassium arrest.

Adenosine Triphosphate↗

Role of procaine and washed red cells in the isolated dog heart perfused at 5 degrees C.

Isolated dog hearts were perfused for 24 hours at 5 degrees C with one of three solutions: plain Krebs solution, Krebs solution containing 167 mg/L of procaine hydrochloride, or Krebs-procaine solution with washed red cells (hematocrit 2%). Coronary vascular resistance (CVR) of hearts perfused with Krebs solution alone increased sharply between the eighth and the twelfth hours of perfusion and then stabilized. Increase of myocardial firmness paralleled the increase of CVR. The addition of procaine to Krebs perfusate kept the heart flaccid and suppressed the steplike increase in CVR but failed to improve significantly the preservation of the hearts. The addition of washed red cells to Krebs perfusate kept CVR near baseline level, improved coronary perfusion flow, doubled myocardial oxygen consumption, reduced edema formation, and improved left ventricular stroke work (LVSW) of the preserved heart. This improvement seems mostly related to a mechanical effect of red blood cells on capillary flow distribution of the heart.

Animals↗