Expression of slow skeletal troponin I in adult mouse heart helps to maintain the left ventricular systolic function during respiratory hypercapnia.
Compared with the adult, neonatal heart muscle is less sensitive to deactivation by acidic pH. We hypothesized that expression of slow skeletal troponin I (ssTnI), the embryonic isoform, in adult heart would help maintain left ventricular (LV) systolic function during respiratory hypercapnia. We assessed LV function by transthoracic 2D-targeted M-mode and pulsed Doppler echocardiography in transgenic (TG) mice in which cardiac TnI was replaced with ssTnI and in nontransgenic (NTG) littermates. Anesthetized mice were ventilated with either 100% oxygen or 35% CO2 balanced with oxygen. Arterial blood pH with 35% CO2 decreased to the same levels in both groups of animals. In the absence of propranolol, the LV fractional shortening was higher in TG compared with NTG mice throughout most of the experimental protocol. LV diastolic function was impaired in TG compared with NTG mice both at 100% oxygen and 35% CO2 because E-to-A wave ratio of mitral flow was significantly lower, and E-wave deceleration time and LV isovolumic relaxation time were longer in TG compared with NTG mice. When compensatory mechanisms that occur through stimulation of beta-adrenergic receptors during hypercapnia were blocked by continuous perfusion with propranolol, we found that NTG mice died within 3 to 4 minutes after switching to 35% CO2, whereas TG mice survived. Our experiments demonstrate the first evidence that specific replacement of cardiac TnI with ssTnI has a protective effect on the LV systolic function during hypercapnic acidosis in situ.
Urboniene
Dalia
D
Center for Cardiovascular Research, Department of Physiology and Biophysics, Section of Cardiology, University of Illinois at Chicago, IL 60612, USA.
Dias
Fernando A L
FA
Peña
James R
JR
Walker
Lori A
LA
Solaro
R John
RJ
Wolska
Beata M
BM
D000138:Acidosis / Q000503:physiopathology; D000818:Animals; D001784:Blood Gas Analysis; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003971:Diastole; D005260:Female; D006935:Hypercapnia / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation; D011433:Propranolol / Q000494:pharmacology; D013599:Systole; D019210:Troponin I / Q000235:genetics / Q000502:physiology*; D016277:Ventricular Function, Left; D000099211:Phospholamban
D002118:Calcium; D002135:Calcium-Binding Proteins; D011433:Propranolol; D019210:Troponin I; D000099211:Phospholamban