Background: Structural and functional changes involved in cardiac injury induced by diabetes mellitus, pressure-overload, or both conditions were evaluated.
Methods: Pressure-overload was established by suprarenal aortic banding in rats. Six weeks later, diabetes was induced by streptozotocin (STZ, 65 mg/kg, intraperitoneally), resulting in four groups: SHAM, banded (BA), diabetic (DM), and diabetic-banded (DM-BA). On the 12th week, left ventricular (LV) structure and function were evaluated. LV function was assessed in vivo with pressure-volume catheters and in vitro by papillary muscles' performance at baseline and in response to isoprenaline (ISO, 10(-8) to 10(-5) M).
Results: Compared to SHAM, we observed a significant increase of type-B natriuretic peptide (BA = 370 +/- 110%; DM-BA = 580 +/- 210%), LV mass (BA = 36.8 +/- 3.6%; DM-BA = 32.1 +/- 3.1%), cardiomyocyte diameter (BA = 19.5 +/- 2.3%; DM = 14.3 +/- 1.9%; DM-BA = 11.4 +/- 2.0%), fibrosis (BA = 85 +/- 14%; DM = 145 +/- 28%; DM-BA = 155 +/- 14%), advanced glycation end-product (AGE) deposition (DM = 141 +/- 29%; DM-BA = 166 +/- 46%), contraction (tAT: DM = 13.7 +/- 2.4%; DM-BA = 26.3 +/- 7.1%); a delayed relaxation (tHR: DM = 13.8 +/- 2.6%; DM-BA = 25.5 +/- 9.2%) and a decrease of collagen type-I/type-III ratio (DM = -66.1 +/- 4.6%; DM-BA = -51.9 +/- 5.5). In SHAM animals, ISO (10(-5) M) increased 86.5 +/- 26.2% active tension, 105.3 +/- 20.2% dT/dt(max), and 166.8 +/- 29.9% dT/dt(min). Similar effects were observed in BA and DM animals, whereas in DM-BA these inotropic and lusitropic responses were blunted. Moreover, at a similar resting muscle length, ISO decreased passive tension by 12 +/- 3% in SHAM and 11 +/- 3% in BA, indicating an increase in myocardial distensibility, an effect that was absent in both diabetic groups.
Conclusion: Long-standing pressure-overload increased LV mass, while diabetes promoted AGE and collagen deposition, which might explain the abolition of ISO-induced increased myocardial distensibility. Association of pressure-overload and diabetes completely blunted the inotropic and lusitropic responses to ISO, with no additional structural damages than in pressure-overload or diabetes alone.