Particle-induced coronary vasoconstriction during cardioplegic infusion. Characterization and possible mechanisms.
We have characterized an isolated rat heart preparation in which particles induce transient coronary vasoconstriction. Exploiting the fact that all commercially available intravenous solutions contain permissible levels of contaminant particles (usually 2 to 20 micron in diameter), we investigated whether these particles have any adverse effect upon coronary flow. A commercially available intravenous solution was modified to produce the St. Thomas' Hospital cardioplegic solution. Constant-pressure infusion of this solution over a 20 minute period caused a 46.2% +/- 5.1% reduction in coronary flow. This flow impairment could be limited to 13.3% +/- 3.5% by the incorporation of a 0.8 micron in-line filter. In hearts perfused with particle-containing solution followed by ultrafiltered solutions, the impairment of coronary flow was reversed within 1 minute. This quick reversal indicates that the particles were impairing flow not by physical occlusion of vessels but by triggering some form of transient vasoconstriction. In studies with filters of varying porosity (between 0.8 and 15.0 micron), the phenomenon was shown to be attributable to relatively small numbers of particles greater than 10.0 micron in diameter. In studies of myocardial protection, it was shown that the impairment of solution delivery and distribution caused by particles could severely reduce the protective properties of a chemical cardioplegic solution; hearts subjected to 180 minutes of hypothermic (20 degrees C) ischemic arrest with multidose (3 minutes every 30 minutes) cardioplegia recovered almost completely upon reperfusion if a filtered (0.8 micron) solution was used, but failed to recover when unfiltered, commercially prepared solutions were used. In an attempt to define the mechanisms underlying the particle-induced vasoconstriction, we conducted dose-response studies in which various vasoactive agents were used in an attempt to combat the effects of the particles. At their optimal concentrations, procaine (10.0 mmol/L), nifedipine (0.1 mumol/L), and adenosine triphosphate (1.0 mmol/L) completely prevented the problem; lidocaine and dipyridamole partially alleviated the effect; verapamil and isosorbide dinitrate were ineffective. These results indicate that several mechanisms acting at a small vessel level might contribute to the particle-induced vasoconstriction.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology; D004176:Dipyridamole / Q000494:pharmacology; D004340:Drug Contamination; D005374:Filtration; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D009566:Nitrates / Q000494:pharmacology; D010316:Particle Size; D011189:Potassium Chloride / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
D000779:Anesthetics, Local; D001639:Bicarbonates; D002121:Calcium Channel Blockers; D009566:Nitrates; C041711:St. Thomas' Hospital cardioplegic solution; D012965:Sodium Chloride; D004176:Dipyridamole; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D008274:Magnesium; D002122:Calcium Chloride