Biomedical subjects

T J Rohs

Publications and source records attributed to T J Rohs.

4 recordsLinked to original sources

PubMed1998

Postischemic function and protein kinase C signal transduction.

BACKGROUND: The protective effects of myocardial preconditioning may occur by way of multiple mechanisms, with G-protein-mediated protein kinase C (PKC) translocation as a final common pathway. In this study we investigate the pharmacologic induction of preconditioning, by PKC translocation, using PKC agonists/antagonists to reveal its effects on contractile function after myocardial ischemia. METHODS: Langendorff-perfused rabbit hearts received: (1) control; (2) dimethyl sulfoxide (vehicle); (3) acetylcholine (0.55 mmol/L; PKC agonist); (4) 1,2-s,n-dioctanoylglycerol (DOG; 22 mmol/L; PKC agonist); (5) chelerythrine (0.8 mmol/L; PKC antagonist); or (6) DOG-chelerythrine followed by a 2-hour ischemic period, using modified St. Thomas cardioplegia and a 45-minute reperfusion period. The period of ischemia was chosen so as to allow for improvement by appropriate agonists. To observe metabolic changes, tissue nucleotides and nucleosides were measured. Membrane and cytosolic fractions of PKC were determined by an anti-PKC antibody directed against the PKC delta isozyme. Lactate levels and myocardial pH were measured. RESULTS: The PKC agonists DOG and acetylcholine showed the greatest recovery of developed pressure (68% +/- 2%, 60% +/- 9%, respectively). Although pH, lactate, and nucleotide levels were similar between groups at all times, myocyte PKC translocation demonstrated 25% of PKC delta isoforms on cell membrane sites during baseline, which shifted to 67% delta 17% with unprotected ischemia. DOG mimicked this shift with 58% delta 12% of PKC delta isoforms on membranes, which was also blocked by chelerythrine to 35% +/- 7%. CONCLUSIONS: These data demonstrate that PKC translocation results in improved postischemic function, not by alteration of energetics or metabolism, and deserves further investigation.

Acetylcholine↗

PubMed1997

Reperfusion adequacy and functional recovery.

Ischemic myocardium undergoes many physiologic changes, including alterations in contractile function, histologic condition, and oxygen utilization. Reperfusion of ischemic myocardium may reverse some of these changes; however, the level of reperfusion needed for adequate functional recovery, as opposed to myocyte salvage, remains controversial. This study examines the effects of varying levels of reperfusion following ischemia on functional parameters of recovery. Isolated rabbit hearts were subjected to global ischemia at 37 degrees C for 10, 20, or 45 min. The hearts were reperfused at either mean normal baseline pressure (80 mm Hg), one half baseline (40 mm Hg), or one fourth baseline (20 mm Hg). With reperfusion, although all hearts retained the compensatory metabolic ability to upregulate oxygen extraction, reduction of reperfusion pressure resulted in depression of contractility and myocardial oxygen consumption, especially with low-pressure reperfusion. These findings suggest that all levels of reperfusion are not equal for optimal myocardial functional recovery. As minimal reperfusion may result in persistent stunning of myocardium, other means of enhancing reperfusion, such as percutaneous transluminal coronary angioplasty or coronary artery bypass grafting, should be considered.

Angioplasty, Balloon, Coronary↗

PubMed1996

Perfluorocarbon supplementation and postischemic cardiac function.

BACKGROUND: During induced ischemia for cardiac surgery inefficient anaerobic energy mechanisms predominate. Sustaining aerobic metabolism with perfluorocarbon-supplemented blood cardioplegia theoretically could lead to improved postischemic recovery. Therefore we studied functional recovery after myocardial ischemia, comparing perflubron (C8F17Br) supplemented blood cardioplegia to standard blood cardioplegia. METHODS: Nineteen dogs underwent 15 minutes of 37 degrees C global ischemia on cardiopulmonary bypass, followed by 90 minutes of cardioplegic arrest by use of blood cardioplegia with or without perflubron and then 30 minutes of 37 degrees C reperfusion. During ischemia myocardial oxygen tension, temperature, and pH were measured. Postischemic left ventricular recovery was assessed by means of preload recruitable stroke work, exponential end-diastolic stress-strain regression, and preservation of adenosine triphosphate and energy charge. RESULTS: The addition of perflubron, a new shorter half-life, lecithin-emulsified perfluorocarbon, provided superior myocardial protection when compared with standard blood cardioplegia. This benefit was evidenced by significantly increased recovery of preload recruitable stroke work slope (71% +/- 8% versus 42% +/- 9%), decreased myocardial edema, and enhanced end ischemic myocardial oxygen and pH levels. CONCLUSIONS: The reliable oxygen delivery system and endothelial-preserving properties of the perfluorocarbons may prove to be an invaluable asset in addition to standard blood cardioplegia in the preservation of postischemic ventricular function. These data support the further investigation of perfluorocarbon-enriched blood cardioplegia.

Animals↗

PubMed1995

The regional effect of retrograde cardioplegia in areas of evolving ischemia.

Retrograde cardioplegia (RCP) is often used for myocardial protection during coronary bypass grafting, but the regional effect of RCP in areas of evolving ischemia is unknown. We examined the functional and metabolic indices of regional myocardial preservation following acute coronary occlusion with evolving ischemia in a canine model. Following the institution of 37 degrees C cardiopulmonary bypass in 14 dogs, the left anterior descending artery (LAD) was occluded for 15 min. The hearts were then subjected to 90 min of cardioplegic arrest (12 degrees C, 15 mL/kg every 30 min). Seven had antegrade cardioplegia (ACP) alone, while seven had ACP until arrest, then RCP. No topical cooling was used. The LAD occlusion was released after the first bolus of cardioplegia. Regional temperature and pH were measured in the LAD and circumflex (nonischemic) distributions. After 90 min of ischemia and 30 min of reperfusion, all dogs were weaned from bypass. Postischemic function was determined globally by the return of developed pressure (%dP/dt) and regionally by ultrasonic wall crystals. End-ischemic ATP preservation in the LAD distribution was assessed by HPLC (mm ATP/mg protein). Results show that regional functional and metabolic indices were better maintained with RCP in the ischemic LAD distribution. Although only moderate reduction of global function was seen with ACP, the severe reduction noted in LAD regional wall motion with ACP reflects poor regional protection that can be significantly improved in evolving ischemia with RCP.

Animals↗