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Despite improvements in operator technique, catheter technology, and the development of new devices, emergency coronary artery bypass grafting (CABG) is still required in 1%-4% of attempted catheter based revascularization procedures. Patients who require such emergency CABG after failed percutaneous transluminal coronary angioplasty (PTCA) have worse acute outcomes than those undergoing elective CABG, with a higher incidence of Q wave myocardial infarction (MI) and a higher operative mortality. In patients with otherwise refractory abrupt closure, maintenance of antegrade coronary blood flow using perfusion catheters lessens the incidence of Q wave MI and lowers peak creatinine phosphokinase. Direct maintenance of coronary flow thus appears to provide more definitive control of myocardial ischemia than purely adjunctive measures, such as intra-aortic balloon pumping, cardiopulmonary support, or coronary sinus retroperfusion. Although the recent introduction of coronary stents holds great promise for definitive percutaneous reversal of abrupt closure and a dramatic decrease in the incidence of emergency CABG for failed PTCA, maintenance of antegrade flow via perfusion technology remains the cornerstone of management in reducing the perioperative mortality and morbidity of patients who still require emergency bypass surgery after failed PTCA.

Endothelin is a potent vasoconstrictor and a positive inotropic agent in myocardium. Endothelin has been reported to increase myocardial contractility with little or no increase in intracellular Ca2+, thus apparently enhancing myofilament responsiveness to Ca2+. We investigated the effects of endothelin on tension development and Ca2+ responsiveness in both intact and saponin-skinned ferret right ventricular papillary muscles. Isolated ferret papillary muscles were stimulated for 2 h in the presence or absence of endothelin (100 nM). The muscles were then chemically skinned with saponin and exposed to relaxing and contracting solutions containing varying amounts of Ca2+, and the developed force of contraction was measured. The [Ca2+] required for half-maximal activation (pCa50) was determined by fitting force versus Ca2+ data to the Hill equation. In isometrically contracting muscles, endothelin (100 nM) caused a mean percent increase in developed tension of 34.7% +/- 11.3% (mean +/- S.E.). In muscles that were exposed to endothelin for 2 h and then skinned, neither the pCa50 nor the maximal Ca(2+)-activated force (Fmax) were significantly different from control skinned papillary muscles. After skinning, when endothelin (100 nM) was added to the Ca2+ buffers, both pCa50 and Fmax were significantly decreased. When papillary muscles were pretreated with phorbol 12-myristate 13-acetate (PMA) and then skinned, there was a significant increase in the pCa50. These results indicate that endothelin acts directly on the myofilaments to impair force development by directly decreasing the Ca2+ responsiveness of myofilaments.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Profound reduction in antegrade epicardial coronary flow with concomitant ischemia is seen occasionally during percutaneous coronary intervention despite the absence of evident vessel dissection, obstruction, or distal vessel embolic cutoff. In a prior small series of cases, this "no-reflow" phenomenon appeared to be promptly reversed by the intra-coronary administration of verapamil., Methods and Results: To further understand the prevalence of this syndrome and its responsiveness to the proposed therapy, we reviewed 1919 percutaneous interventions performed between January 1991 and April 1993. During the study period, 39 patients (2.0%) met our criteria for no reflow, 37 of whom were treated with intracoronary nitroglycerin followed by intracoronary verapamil and 2 of whom received intracoronary nitroglycerin alone. An additional 16 patients (0.8%) were given verapamil as part of the management of a flow-limiting dissection or distal embolus (mechanical obstruction). Intracoronary verapamil (50 to 900 micrograms, total dose) improved TIMI flow grade in 89% of no-reflow patients and markedly reduced the number of cineframes between contrast injection and opacification of a selected distal landmark (from 91 +/- 56 to 38 +/- 21 frames, P < .001). By contrast, only 19% of patients with epicardial mechanical obstruction showed improvement in TIMI flow grade after verapamil, with minimal reduction in frames to opacification (from 107 +/- 42 to 101 +/- 69, P = .73)., Conclusions: The no-reflow phenomenon--reduction in distal flow without apparent dissection or distal embolization--occurs in 2% of coronary interventions. It generally responds promptly to intracoronary verapamil administration, suggesting that distal microvascular spasm may be its etiology.

The purpose of the present study was to determine the maximal coronary flow reserve (CFR) before and after the administration of successive cocaine doses (0.1, 0.5, 3, and 7 mg/kg IV) for 2 minutes at 10-minute intervals in eight miniature swine. CFR was assessed by the administration of adenosine (0.03, 0.3, and 3 mg IC). Hemodynamic and flow measurements were performed 3 minutes after each dose. Coronary flow (CF) was measured with a Doppler-tipped wire in the proximal left anterior descending coronary artery (LAD). Also, microvessels were dissected, and vessel diameters were measured by a videoelectronic dimension analyzer. In vivo, LAD CF increased fourfold, CFR increased twofold, and coronary vascular resistance (CVR) decreased fourfold after the administration of adenosine. In contrast, LAD CF decreased threefold, CFR decreased onefold, and CVR increased sixfold 3 minutes after the administration of cocaine. Adenosine (3 mg) was repeated 4 minutes after the administration of cocaine, and LAD CF increased 1.4-fold, CVR increased 2.5-fold, and CFR decreased onefold. Thus, adenosine partially reversed the potent cocaine constrictor effect. In vitro, 10(-9) mol/L cocaine decreased the diameter of the coronary microvessels from 129 +/- 12 to 127 +/- 12 microns, and 10(-4) mol/L cocaine decreased coronary microvessel diameter to 114 +/- 15 microns (P < .05). In conclusion, cocaine in vivo decreases CFR, and consistent with the in vivo effect, cocaine in vitro produced constriction of vessels < 200 microns. These results indicate that cocaine can produce profound microvascular spasm. This may contribute to the ischemia/infarction reported in patients who abuse cocaine and who are subsequently found to have normal epicardial coronary arteries.