Effects of formaldehyde on cardiovascular system in in situ rat hearts.
The aim of the present study was to examine the effects of formaldehyde solution on rat left ventricular function and compare it with those in hypertrophic hearts treated with isoproterenol by pressure-volume measurements with the catheter method. After 20-30 min. of intravenous infusion of 3.7% formaldehyde solution (FA) at 10 μl (3.7 mg)/kg/min, normal and hypertrophic hearts showed significant decreases in left ventricle end-systolic pressure (ESP), heart rate and cardiac output per minute, indicating an acute pumping failure. Hypertrophic hearts showed significantly smaller ESP, stroke volumes and cardiac output than those in normal hearts. Systolic pressure-volume area at midrange left ventricular volume (PVA(mLVV) : a mechanical work capability index) was significantly smaller than that in normal hearts and per cent of mean PVA(mLVV) versus pre-infusion mean value in hypertrophic hearts was significantly decreased compared to normal hearts 30 min. after FA infusion. The marked decrease in pH, base excess and no changes in PaO₂ and PaCO₂ suggest metabolic acidosis. The correction of metabolic acidosis with 9% NaHCO₃ did not influence on the acute pumping failure, indicating that metabolic acidosis did not cause it. Ultrastructural observations revealed marked dilation of the sarcoplasmic reticulum with intact sarcolemmal membranes and no disintegration of muscle myofibrils. Ryanodine receptors and calcium (Ca²⁺) pumps (SERCA2A) located in the sarcoplasmic reticulum have major roles in the cytosolic Ca²⁺ handling. Taken together, acute pumping failure by FA may derive from the impairment of Ca²⁺ handling in the cardiac excitation-contraction coupling.
Takeshita
Daisuke
D
Department of Physiology II, Nara Medical University, Kashihara, Japan.
Nakajima-Takenaka
Chikako
C
Shimizu
Juichiro
J
Hattori
Hiroshi
H
Nakashima
Tamiji
T
Kikuta
Akio
A
Matsuyoshi
Hiroko
H
Takaki
Miyako
M
D000818:Animals; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000188:drug therapy / Q000503:physiopathology; D056966:Excitation Contraction Coupling; D005557:Formaldehyde / Q000633:toxicity*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*
D019837:Ryanodine Receptor Calcium Release Channel; D005557:Formaldehyde; D007545:Isoproterenol; D002118:Calcium