The effects of hypocapnic alkalosis on the myocardial contractility of isovolumic perfused rabbit hearts.
During acute respiratory alkalosis myocardial contractility first increases but then decreases towards control levels. The mechanism of this response was investigated in isovolumic perfused rabbit hearts. Developed pressure (DP) and its first derivative (dP/dt) were measured before, during and after hypocapnia induced by equilibrating the perfusate with 2% CO2 rather than the 5% used in control. pH of the perfusate (pHo) changed from 7.36 +/- .02 to 7.71 +/- .01. After about 20 s, an increase in DP of about 20% was detected. This increase in contractility is followed by a partial recovery towards control levels. After the partial recovery a new mechanical steady state is reached in about 2 min. Neither 5-[N-ethyl-N-isopropyl]amiloride (EIPA) 10(-6) M, a blocker of the Na+/H+ exchanger, nor 4,4'-diisothiocyanatostilbene-2-2'-disulfonic acid (SITS) 10(-4) M, or 5-[aminosulfonyl]-4-chloro-2-[(2-furanylmethyl)-amino] benzoic acid (furosemide) 10(-4) M, blockers of Cl-/HCO3- exchanger, abolished the recovery in contractility towards control levels. The recovery was not abolished by replacing 50% of extracellular Cl- concentration by either sulfate or gluconate. The lack of blockade of this mechanical recovery in spite of the intervention performed suggests a mechanism other than the exchangers as the cause of the biphasic changes.
Mosca
S M
SM
Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Argentina.
Gelpi
R J
RJ
Borelli
R
R
Cingolani
H E
HE
D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000472:Alkalosis, Respiratory / Q000503:physiopathology*; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D005665:Furosemide / Q000494:pharmacology; D016857:Hypocapnia / Q000503:physiopathology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D010477:Perfusion; D011817:Rabbits; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors
D017923:Sodium-Hydrogen Exchangers; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D000584:Amiloride; D005665:Furosemide; C039614:ethylisopropylamiloride