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Ultrastructural evidence of increased tolerance of hibernating myocardium to cardioplegic ischemia-reperfusion injury

José Milei, MD, PhD^*, César G. Fraga, PhD, Daniel R. Grana, VMD^*, Ricardo Ferreira, MD and Giuseppe Ambrosio, MD, PhD, FACC^,*

^* Instituto de Investigaciones Cardiológicas (ININCA), Department of Medicine, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina
Department of Physical Chemistry-PRALIB, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
Hospital Militar Central, Cirugía Cardiovascular, Buenos Aires, Argentina
Division of Cardiology, University of Perugia School of Medicine, Perugia, Italy

View larger version (133K): [in a new window]   Figure 1 Representative electron micrographs of biopsies taken before cardiac arrest from non-contracting areas of the anterior wall in two hibernation patients (magnification x 8,000). (A) Loss of contractile material in the vicinity of the nucleus (bottom right); sarcoplasmic reticulum is absent, as well as T-tubules. This space is filled with amorphous material (*). Only two rows of regularly arranged sarcomeres are visible. Small mitochondria are scattered throughout the cytoplasm, intermingled with irregularly shaped mitochondria; mitochondrial structure is preserved. A tortuous nucleus projecting (arrow) into the cytoplasm is observed. (B) Marked sarcomere disorganization, with abnormal Z-bands.

View larger version (152K): [in a new window]   Figure 2 Effects of ischemia-reperfusion. (A) Normally contracting area of the anterior wall (control patient) before cardiac arrest (x10,000). Note overall preservation of structure. Sarcomeres are in register; mitochondria show normal morphology with tightly packed cristae and intact membranes. Sarcolemma is preserved. (B) Normally contracting area of the anterior wall (control patient) 10 min after reperfusion (x10,000). Note intracellular and intermyofibrillar edema; mitochondria appear massively swollen, with alteration of cristae and frequent disruption of inner and outer membranes. (C) Non-contracting area of the anterior wall (hibernation patient) before cardiac arrest (x12,000). Sarcoplasmic reticulum is scarce, substituted by amorphous material. Some mitochondria show mild edema. (D) Non-contracting area of the anterior wall (hibernation patient) 10 min after reperfusion (x8,000). Mitochondria are well-preserved, and only mild edema is observed. RS = residual sarcomeres.

View larger version (37K): [in a new window]   Figure 3 Mitochondrial score of biopsies taken from either hibernating segments (hibernation), or from normally contracting myocardium (control), before cardiac arrest, or 10 min after reperfusion. Grading scale was: 0 = normal; 1 = initial swelling (separation of cristae, decreased matrix density); 2 = more marked swelling than in grade 1; 3 = massive swelling with architectural disruption; and 4 = findings as in grade 3 plus rupture of inner and outer mitochondrial membranes. Note the shift from normal appearance to altered morphology occurring with ischemia and reperfusion. This shift is less pronounced in biopsies from hibernating segments. Data are mean ± SE of percent mitochondria scored. Values in parentheses are the number of mitochondria scored for each set. *p < 0.05 vs. control.