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Biomedical subjects

M K Pasque

Publications and source records attributed to M K Pasque.

At least 55 records · Page 3Linked to original sources
PubMed1991

The evolution of single lung transplantation for emphysema. The Washington University Lung Transplant Group.

Classic transplantation dogma mandated bilateral lung replacement for lung transplant candidates with end-stage emphysema to avoid air trapping in the native lung and subsequent crowding of the newly transplanted lung. During a recent 12-month period 11 patients with emphysema received a single lung transplant. There was no hospital mortality and only one patient had any notable degree of air trapping in the native lung. Substantial improvement in pulmonary function was seen as early as 2 weeks after transplantation, with significant functional improvement seen by 6 weeks, despite some residual ventilation-perfusion mismatch. We have demonstrated the utility and safety of single lung transplantation for patients with end-stage emphysema, and it is our operation of choice in recipients more than 50 years of age.

Exercise Test↗
PubMed1990

Improved technique for bilateral lung transplantation: rationale and initial clinical experience.

We previously described a technique for en bloc double-lung transplantation that was initially applied to select patients with cystic fibrosis and emphysema. This procedure is quite complex and associated with several limitations, including a substantial incidence of airway ischemia, postoperative myocardial depression, and cardiac denervation. To address these problems we have developed a simpler procedure for replacing both lungs. The operation is done through a transverse thoracosternotomy and involves sequential replacement of the two lungs. Positive features include separate bronchial anastomoses to reduce ischemic airway complications, elimination of the need for total cardiopulmonary bypass and a period of ischemic cardiac arrest, improved exposure to reduce intraoperative and postoperative hemorrhage, and maintenance of cardiac innervation. Additionally, the technique can be more easily mastered and widely applied. Details of the procedure and its initial clinical application in 3 patients having emphysema, cystic fibrosis, and bronchiolitis obliterans following previous double-lung transplantation, respectively, are described. All 3 patients recovered without complication. Postoperative function was excellent in spite of lung ischemic times ranging up to 91/2 hours.

Adult↗
PubMed1989

Internal mammary artery grafts: the shortest route to the coronary arteries.

Inadequate length can limit the use of the internal mammary artery (IMA) for coronary revascularization. By following the shortest route from its origin to the recipient coronary artery, IMA use can be maximized. Seven cadavers were studied to determine that shortest route for the left and right IMAs. The shortest route for the left IMA to the left anterior descending coronary, diagonal, and circumflex coronary arteries was through the pericardium (p less than or equal to 0.01). For the right IMA, the significantly shortest routes were across the anterior heart for the left anterior descending and diagonal arteries, through the right pericardium for the right coronary artery or posterior descending artery, and through the pericardium and transverse sinus for the circumflex artery. Thus, any coronary artery can be reached with an in situ IMA, and the route through the pericardium is markedly shorter to ipsilateral coronary arteries.

Coronary Vessels↗
PubMed1989

Single lung transplantation for severe chronic obstructive pulmonary disease. Washington University Lung Transplant Group.

Single lung transplantation (SLT) has been considered physiologically inappropriate for patients with chronic obstructive pulmonary disease (COPD). It has been postulated that the high static compliance and elevated pulmonary vascular resistance of the native lung functioning in parallel with the more normal allografted lung could cause unacceptable ventilation-perfusion mismatching and/or overinflation of the native lung with encroachment on the expansion of the transplanted lung. While some degree of ventilation-perfusion imbalance may be physiologically obligatory after SLT for COPD, a significant disruption in gas exchange may not occur unless a complication, such as rejection or infection, arises in the transplanted lung. A 60-year-old man with COPD who underwent successful SLT is presented and discussed. In spite of scintigraphic evidence of ventilation-perfusion mismatching between the native lung and the allograft during the first six postoperative weeks, the recipient had normal resting gas exchange on room air after the second postoperative week. Fourteen weeks after transplantation, his maximum oxygen uptake was 37.3 percent of the predicted maximal value, and no evidence of ventilatory limitation was detected. His functional status and lifestyle have been markedly improved by SLT. The role of SLT for COPD should be reconsidered. It may be a reasonable transplantation alternative for selected patients with COPD who are not candidates for double lung transplantation (DLT).

Exercise↗
PubMed1989

Reduction of sternal infection by application of topical vancomycin.

Sternal or mediastinal infection after heart operations occurs infrequently but carries a high cost in money, morbidity, and mortality. At our hospital, Staphylococcus nonaureus causes most of these infections and is uniformly sensitive to vancomycin. In a prospective study of 416 patients having cardiac operations, randomized by hospital record number, topical vancomycin was applied to the cut sternal edges in 223 patients (group V) and was omitted in the control group (C) of 193 patients. The vancomycin was applied in a hemostatic paste of topical thrombin and powdered absorbable gelatin; in the control group only the hemostatic paste was applied. All patients received prophylactic systemic antibiotics for 2 days. Sternal infection occurred in one patient in group V (0.45%) and in seven patients in group C (3.6%) (p = 0.02). Infection also correlated with longer operative times (p = 0.027). By multivariate testing, vancomycin (p = 0.013) and shorter operative times (p = 0.014) independently predicted reduced infection rates. In the one patient with an infection in group V, Staphylococcus aureus was cultured; this organism was also cultured in two patients in group C, with Staphylococcus nonaureus being the culprit in the other five patients with sternal infections in group C. Topical vancomycin applied to the cut sternal edges reduces the risk of postoperative sternal infection.

Administration, Topical↗
PubMed1988

Assessment of the intrinsic contractile status of the heart during sepsis by myocardial pressure-dimension analysis.

The effect of sepsis on the intrinsic contractile status of the myocardium is best examined in the awake, closed-chest animal with intact circulation because anesthesia, open thoracotomy, and circulatory support are all known to affect hemodynamics. To fulfill these criteria, 18 adult dogs were chronically studied in the awake state after instrumentation with left ventricular high-fidelity pressure catheters and ultrasonic dimension transducers to measure left ventricular transmural pressure and minor axis dimension. This allowed computer assessment of the left ventricular end-systolic pressure-dimension relationship in the control state and at intervals following cecal ligation in one group of dogs. A second group of control animals was studied over variable time intervals without cecal ligation to evaluate the temporal stability and reproducibility of the animal model and the end-systolic pressure-dimension relationship. Evaluation of contractility by use of the end-systolic pressure-dimension relationship was essential because this relationship is a sensitive indicator of the intrinsic myocardial contractile state while remaining insensitive to the wide swings in preload and after load that are commonly seen in sepsis. In the control group of dogs, the temporal consistency and stability of the end-systolic pressure-dimension relationship in this model was confirmed; no significant changes in the slope and dimension-axis intercept were demonstrated over the study interval. In the septic group of dogs, however, the intrinsic myocardial contractility significantly deteriorated as the mean slope of the end-systolic pressure-dimension relationship (mmHg/mm) decreased from 16.87 +/- 0.85 to 12.79 +/- 1.67 over 120 hours following cecal ligation. Intrinsic contractility of the heart during sepsis was therefore isolated for the first time from the widely variant loading conditions seen during sepsis by pressure-dimension analyses in the chronically instrumented, awake, closed-chest canine with intact circulation.

Animals↗
PubMed1988

Fontan hemodynamics.

Right atrial-pulmonary artery connection places the pulmonary circulation in series with the systemic circulation rather than the single ventricular "parallel" circulatory arrangement that usually is present prior to repair. The accompanying central cardiac shunt and volume overload physiology are eliminated. Favorable changes in ventricular dimension, ventricular wall stress, cardiovascular efficiency, relative systemic perfusion, and arterial oxygen saturation should result. The ongoing myocardial injury associated with the single-ventricle volume overload is presumably arrested and repair is initiated to a variable degree. Some candidates for right atrial-pulmonary artery connection may not benefit from repair because of irreversible ventricular injury. More accurate indices of systolic and diastolic ventricular function should be applied to this difficult group of borderline patients to further define potential for myocardial recovery and, therefore, candidacy for Fontan repair.

Anastomosis, Surgical↗
PubMed1984

Effects of delay in administration of potassium cardioplegia to the isolated rat heart.

Ischemic injury to the heart in the period between aortic cross-clamping and administration of cardioplegic solution was evaluated in the normothermic rat heart model. After isolation and control perfusion with oxygenated Krebs-Henseleit bicarbonate buffer, the hearts were given lactated Ringer's cardioplegic solution (30 mEq of K+ per liter) for 2 minutes at three different intervals following aortic clamping: no delay, 2-minute delay, and 5-minute delay. Thereafter, the hearts were left unperfused and the time to initiation of ischemic contracture was recorded. Adenosine triphosphate (ATP) and creatine phosphate levels were measured in all groups prior to and at the conclusion of cardioplegia administration. A 2-minute delay in the administration of cardioplegic solution resulted in significantly lower (p less than 0.001) ATP levels that were restored after 2 minutes of cardioplegia administration. Contracture times were not significantly altered. A 5-minute delay resulted in significantly shorter (p less than 0.001) contracture times and significantly lower (p less than 0.001) ATP levels that were not restored to preischemic levels by 2 minutes of cardioplegia administration. The fate of the myocardium may be insensitive to events that occur during the earliest moments of ischemia provided that rapid administration of oxygenated potassium cardioplegia follows the ischemic period and restores preischemic high-energy phosphate stores. However, there is a critical ischemic time during the initial interval before cardioplegia that is associated with an impaired ability of the myocardium to tolerate subsequent ischemia.

Adenosine Triphosphate↗
PubMed1984

Metabolic intervention to affect myocardial recovery following ischemia.

Myocardial recovery during reperfusion following ischemia is critical to patient survival in a broad spectrum of clinical settings. Myocardial functional recovery following ischemia correlates well with recovery of myocardial adenosine triphosphate (ATP). Adenosine triphosphate recovery is uniformly incomplete during reperfusion following moderate ischemic injury and is therefore subject to manipulation by metabolic intervention. By definition ATP recovery is limited either by (1) energy availability and application in the phosphorylation of adenosine monophosphate (AMP) to ATP or (2) availability of AMP for this conversion. Experimental data suggest that substrate energy and the mechanisms required for its application in the creation of high energy phosphate bonds (AMP conversion to ATP) are more than adequate during reperfusion following moderate ischemic injury. Adenosine monophosphate availability, however, is inadequate following ischemia due to loss of diffusable adenine nucleotide purine metabolites. These purine precursors are necessary to fuel adenine nucleotide salvage pathways. Metabolic interventions that enhance AMP recovery rather than those that improve substrate energy availability during reperfusion are therefore recommended. The mechanisms of various metabolic interventions are discussed in this framework along with the rationale for or against their clinical application.

Adenine↗
PubMed1984

Anesthesia-induced myocardial depression: quantitation of effects on systolic and diastolic function.

The effect of general anesthesia induced with halothane and nitrous oxide on left ventricular (LV) contractility and diastolic mechanics was directly assessed in the chronically instrumented canine model. Seven dogs were instrumented with ultrasonic dimension transducers to measure LV diameter and micromanometers to measure LV transmural pressure. Contractility was assessed by the slope (EES) of the end-systolic pressure-diameter relationship PES = EES (LES - LD). Diastolic compliance was assessed by fitting end-diastolic pressure-dimension data to the exponential P = alpha (e beta epsilon L-1), where alpha and beta are nonlinear elastic coefficients. A new index (ID20) that identifies the dose of anesthetic necessary to depress the inotropic state by 20% was calculated to be 0.63% for halothane. Contractility was progressively decreased by halothane, with EES falling from 10.1 +/- 0.6 at control to 6.7 +/- 0.4 at 1% halothane and to 4.2 +/- 0.5 at 2% halothane (p less than 0.05 at each halothane level). However, similar levels of halothane did not significantly alter alpha and beta, nor did they significantly shift the exponential diastolic compliance curve from control. Seven patients who underwent coronary artery bypass grafting conducted under narcotic anesthesia showed a similar halothane-induced depression of contractility; 0.5% halothane decreased EES from 11.5 +/- 2.0 to 8.0 +/- 2.4 (p less than 0.01). Use of ID20 allows reclassification of anesthetic agents in accord with their myocardial depressant effects, which with halothane appears to be caused by decreased inotropism without alterations in diastolic chamber mechanics.

Animals↗
PubMed1984

The comparative effects of dopamine and dobutamine on ventricular mechanics after coronary artery bypass grafting: a pressure-dimension analysis.

To compare the contractile response to dopamine and dobutamine after coronary artery bypass grafting, 20 patients were instrumented with ultrasonic dimension transducers to measure left ventricular anterior/posterior minor-axis diameter and equatorial wall thickness. Micromanometers were placed to measure left ventricular transmural pressure. Pressure-dimension data were recorded and computer analyzed during dopamine and dobutamine infusions in each patient at 0, 2.5, 5.0, and 10.0 micrograms/kg/min 16 to 20 hr after surgery. Contractility was measured by determination of maximal velocity of shortening of the ventricular diameter (mm/sec) and wall excursion (mm). Preload was assessed with end-diastolic diameter and peak left ventricular wall stress (dynes-cm-2) was calculated at each dose. End-diastolic diameter was unchanged at equal doses of dopamine and dobutamine. However, ejection phase indexes of contractility were significantly higher with dobutamine than dopamine, and were associated with lower levels of peak wall stress and peripheral vascular resistance. These data indicate that use of dobutamine results in greater enhancement of left ventricular contractility without the disadvantage of excess demand on myocardial oxygen reserve produced by higher levels of myocardial wall tension. Furthermore, the decreased peripheral vascular resistance induced by dobutamine accounts for some of the differences in drug response, and is beneficial in optimizing myocardial oxygen balance during pharmacologic inotropic support of the bypass graft patient or other patients in whom there is a potential for development of myocardial ischemia.

Angina Pectoris↗
PubMed1983

Myocardial adenosine triphosphate levels during early sepsis.

Myocardial adenosine triphosphate (ATP) levels were determined in rats given sepsis by cecal ligation. Determinations were made after a set time interval, prior to the onset of obtundent effects and immobility, in an attempt to avoid the well-documented, deleterious influence of hypoperfusion status. The absence of a low perfusion state at the time of myocardial biopsy was confirmed by the maintenance of simultaneously determined peripheral organ ATP levels. Myocardial ATP levels were significantly elevated in two groups of septic rats, one minimally hydrated and the other actively hydrated intravenously (IV), when compared with either controls that had not been operated on or animals that underwent sham operations and were IV hydrated. The relationship between elevated myocardial ATP levels and functional status during sepsis deserves further investigation.

Adenosine Triphosphate↗
PubMed1983

The influence of time on the response to dopamine after coronary artery bypass grafting: assessment of left ventricular performance and contractility using pressure/dimension analyses.

Pressure and dimension analyses were used to quantitate the changing cardiac response to dopamine over a 24-hour interval after coronary artery bypass grafting (CABG). Ultrasonic dimension transducers were utilized to measure the minor-axis diameter of the left ventricle, and matched micromanometers were inserted to measure intracavitary left ventricular pressure and intrathoracic pressure. Pressure and dimension data were recorded and analysed by computer during dopamine infusion at 0, 2.5, 5.0, and 10.0 micrograms per kilogram per minute, at periods designated as early (2 to 4 hours after CABG) and late (18 to 24 hours after CABG). Myocardial contractile responses to dopamine (peak velocity of minor-axis shortening, maximal excursion) were similar at each dose in the early and late studies. However, overall hydraulic performance, as reflected by cardiac outputs and the areas of the pressure/diameter work loops, had augmented late dose responses. This study suggests a major change in the relationship between the heart and peripheral control mechanisms that may partially explain diminishing inotropic requirements over time, in addition to the generally accepted occurrence of improvement in contractile state and functional reserve following cardiac operation.

Angina Pectoris↗
PubMed1983

The mechanism of halothane-induced myocardial depression. Altered diastolic mechanics versus impaired contractility.

Although halothane has been shown to depress left ventricular function, it remains a common alternative to narcotic anesthesia in cardiac operations. To clarify the mechanism by which this functional depression occurs (direct decrease in contractility versus altered diastolic compliance), we studied seven dogs in the closed-chest state following instrumentation with ultrasonic dimension transducers to measure left ventricular anteroposterior diameter and micromanometers to measure transmural left ventricular pressure. Ventricular volumes were varied with transient vena caval occlusions in the awake state and following general anesthesia with halothane at 1% and 2% end-tidal concentrations. Ventricular contractility was assessed by the slope of the end-systolic pressure-diameter relationship (EES). Following normalization of end-diastolic diameters with a Lagrangian strain definition (E), diastolic compliance was assessed by fitting end-diastolic pressure-strain data to the exponential: P = alpha (e beta E -1), where alpha and beta are nonlinear elastic coefficients. Halothane was found to produce a significant, dose-dependent decrease in EES from 10.6 +/- 0.6 control to 6.7 +/- 0.4 at 1% halothane and 4.2 +/- 0.5 at 2% halothane (p less than 0.05, control versus both 1% and 2% halothane). Furthermore, halothane at the concentrations studied did not significantly alter alpha and beta nor significantly shift the exponential end-diastolic pressure-strain curve from control. These data indicate that halothane produces a direct, severe depression of left ventricular contractility without primarily altering the diastolic mechanical properties of the myocardium.

Animals↗
PubMed1982

The effect of PEEP on left ventricular diastolic dimensions and systolic performance following myocardial revascularization.

To quantitate the alterations in left ventricular (LV) dimensions and performance at successive levels of positive end-expiratory pressure (PEEP), 16 patients undergoing coronary artery bypass grafting (CABG) underwent instrumentation with ultrasonic dimension transducers to measure the minor-axis diameter of the left ventricle. Matched micromanometers were placed to measure intracavitary LV pressure and intrathoracic pressure. LV pressure and dimension data were recorded and computer analyzed during continuous positive-pressure ventilation at 0, 5, 10, and 15 cm H2O of PEEP 4 to 8 hours postoperatively. Preload was determined by the end-diastolic minor-axis diameter, cardiac output was measured by thermodilution, and indices of LV contractility assessed included the maximal velocity of minor-axis shortening and the slope of the end-systolic pressure-diameter relationship. PEEP produced a progressive increase in intrathoracic pressure associated with a fall in cardiac output; this was associated with a decrease in LV end-diastolic diameter and no significant change in the maximal velocity of minor-axis shortening or the slope of the end-systolic pressure-diameter relationship. Our results indicate that PEEP of 10 cm H2O or greater will produce a significant fall in cardiac output in patients following CABG, due to a decrease in preload rather than impaired LV contractility.

Angina Pectoris↗
PubMed1982

Ribose-enhanced myocardial recovery following ischemia in the isolated working rat heart.

Recovery for myocardial adenosine triphosphate (ATP) following moderate periods of ischemic is dependent upon the availability of adenosine monophosphate (AMP) and diphosphate (ADP) for rephosphorylation. Recovery of AMP and ADP levels following ischemia is, in turn, determined by the rates of salvage and de novo adenine nucleotide synthesis. Phosphoribosyl pyrophosphate (PRPP) availability is rate limiting in both salvage and de novo adenine nucleotide synthesis. Parenteral ribose infusions in rats have been documented to elevate myocardial PRPP levels with resultant enhancement of adenine nucleotide synthesis. In this study postischemic recovery of myocardial function and ATP levels in isolated, working rat hearts given ribose infusions before and after ischemia was compared with recovery in control hearts subjected to the same protocol without ribose administration. The mean percent of functional recovery in control hearts following 15 minutes of warm ischemia reached values of 56.7 +/- 4.1%, 63.5% +/- 4.3%, 65.9% +/- 4.6%, and 70.5% +/- 4.7% at 2, 5, 10, and 15 minutes of work following ischemia. Hearts perfused with ribose demonstrated improved mean percent return of function at similar intervals of postischemic work with values of 67.9% +/- 4.2%, 73.7% +/- 3.7%, 81.0% +/- 3.5% (* = p less than 0.02 versus control) *and 85.4% +/- 3.3%, *respectively. Determinations of myocardial ATP levels (mumoles/gm of dry weight) made at the end of 15 minutes of postischemic work were significantly higher (p less than 0.02) in the ribose-treated hearts (18.9 +/- 0.7) than in controls (16.3 +/- 0.6). Infusion of ribose before and after ischemia is a biochemically logical method of improving postischemic myocardial ATP and functional recovery by manipulation of adenine nucleotide synthetic pathways.

Adenine Nucleotides↗