The afterload dependence of the intracellular calcium transient in isolated working human myocardium was analyzed in both donor and recipient hearts of seven patients undergoing transplantation because of dilated cardiomyopathy. The intracellular calcium transient (recorded by the fura 2 ratio method), force development, and muscle shortening were simultaneously recorded in small (0.6x4.0-mm) electrically driven (60 beats per minute) trabeculas contracting at constant preload against varying afterloads. When the fibers contracted under isometric conditions, the intracellular calcium transients of normal and failing myocardium were similar. However, in dilated cardiomyopathy, stepwise afterload reduction and the concomitant increase in shortening amplitudes were associated with extraordinary alterations in the shape of the calcium transients: the amplitude rose, the time to peak was delayed, and at minimal afterloads, a long-lasting plateau was observed, he intracellular calcium transient of normal human myocardium is modulated during the performance of mechanical work.1)2 The ability to perform mechanical work (to shorten against a given afterload) was depressed in skinned myocardial fibers of patients with dilated cardiomyopathy, although the crossbridge cycling rate was normal.3 The intracellular calcium transient of intact working human myocardium of patients with dilated cardiomyopathy had not yet been analyzed. Measurements of calcium transients during the performance of mechanical work have now become possible, since new fluorescent dyes are available.4-7 For the measurement of intracellular calcium transients, the dual wavelength excitation method ("ratio method") and the fluorescent dye fura 2 were selected to minimize shortening artifacts.',4,6,8 Combined measurements of calcium, force, and shortening show for the first time that extraordinary alterations of the intracellular calcium transient occur in dilated cardiomyopathic myocardium during shortening.
Materials and Methods Muscle SpecimensLeft ventricular myocardium excised from the free ventricular wall was obtained from seven recipient hearts of patients undergoing heart transplantation because of dilated cardiomyopathy. None of the patients had a history of drug addiction or Received August 11, 1993; accepted February 7, 1994 and the diastolic decay was retarded. The calcium-time integral during shortening against passive resting force was 124±5% of the isometric control in normal myocardium and 172±12% in end-stage heart failure (P<.0001). We conclude that adequate interpretation of intracellular calcium transients requires simultaneous recordings of force and shortening. The extraordinary afterload dependence of the calcium transient in end-stage heart failure may be attributed to increased dissociation of calcium from the contractile proteins, a reduced calcium reuptake rate of the sarcoplasmic reticulum, or an increased calcium inflow due to altered permeabilities of the calcium channels during shortening. A potential role of mechano...
Surgical intervention in fulminant pulmonary embolism (PE) is still associated with an overall 30% fatal outcome which increases to about 60% when cardiopulmonary resuscitation (CPR) is necessary. Despite unfavorable conditions like hemodynamic instability, failed lysis or CPR, the surgical strategy might have a certain impact on the patient's outcome since 30-40% of the surgical mortality is related to persistent right heart failure and early thromboembolic recurrence. From 1/88 to 8/94 a total of 25 patients (15 females, 10 men, mean age 57 [25-78]) years underwent emergency pulmonary embolectomy with the use of the heart-lung machine. Seventeen patients were operated upon between 1988 and 1992. A standard approach by central pulmonary artery incision with extraction of adjacent pulmonary emboli using forceps, suction of Fogarty catheters was used. Six of these patients (35%) died, with four out of six operated upon under CPR. Since 1993 we have used a modified surgical strategy in eight patients. Five patients (63%) were operated on after or under CPR. In these cases, left and right pulmonary arteries were incised peripherally and all segmental arteries were desobliterated selectively using small suction devices. Thereafter the right atrium was opened and inspected. After removal of the inferior caval vein cannula all inferior body blood was taken with cardiotomy suction while both legs and the abdomen were massaged centripetally to mobilize additional fresh thrombotic material. In three cases up to 50 cm long thrombi could be delivered. All patients have survived to date with two patients receiving a LGM caval filter placed percutaneously after bilateral postoperative phlebography had revealed ongoing thrombotic disease. We conclude that selective desobliteration of every segmental pulmonary artery in combination with simultaneous clearance of major body veins from additional thrombotic material will probably lower surgical mortality in these critically ill patients.
I) BDM reduced the isometric force development of the electrically driven isolated human myocardial muscle strip in a dose-dependent way.(ABSTRACT TRUNCATED AT 250 WORDS)
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