Anwar Abd-Elfattah S1*, Jian-Huo Guo1, Shi-Ping Gao1, Ahmed Elwatidy F1, Ibrahim Hegab M1, David Salter R1, Mohammad Alfagih R2 and Nermine Abd-Elfattah A1
1Department of Surgery, Virginia Commonwealth University Health System, Virginia, USA
2Prince Sultan Cardiac Center, Riyadh, Saudi Arabia
previously normal subjects and naïve hearts but not in diseased hearts. The current studies have investigated myocardial preconditioning in five clinically relevant models of stunned, infarcted, Spontaneous Hypertrophied (SH) and End-Stage Failing (ESF) hearts. Methods: Global Myocardial Stunning (GMS) was created in dogs, on-pump. Heart performance (Stroke-Work/End diastolic length) was used as a primary end-point. Eight dogs were subjected to six interrupted episodes of Warm Global Aortic Cross-Clamping (WACC) and reperfusion (10 x 10 min) compared to sustained WACC and reperfusion (60 x 60 min). SH dog hearts (n=11) were subjected to GMS, on-pump with or without infusion of adenosine, an IPC memetic. Rabbit model (n=75) of acute Myocardial Infarction (MI) was used to determine the effects of prior acute MI on reinfarction of the same, or remote, vascular bed and whether IPC provides supplementary cardioprotection. Canine model of heart failure (n=33) and UM-X 7.1 strain hamsters (n=28), develops idiopathic dilated cardiomyopathy with age, were used to determine whether IPC limits MI in failing hearts compared to non-failing hearts. Results: In dogs, the first GMS caused ATP depletion (32%) and dysfunction (42%). Five episodes of GMS did not cause cumulative contractile dysfunction (stunning), confirming stunning-induced contractile preconditioning (p<0.05 vs. sustained 60 min GMS). In rabbit model of acute MI, reinfarction of the same vascular bed did not expand the infarct size. Prior acute MI significantly reduced the infarct size in a remote area (p<0.05). Dilated cardiomyopathy canine and hamster hearts had significantly smaller infarct size in the absence of prior IPC. KATP abolished infract size limitation in MI-induced preconditioned hearts. Conclusion: Stunned, infarcted, hypertrophied and failing hearts are perpetually preconditioned and utilizing maximal preconditioning reserve against myocardial stunning or MI. IPC, per se, provides no or limited supplementary cardioprotection in diseased hearts, thus offering the basis of biological explanation for the adaptive response “MEMORY” to ischemic stress and disease.
Ischemic preconditioning; Myocardial stunning; Infarction; Re-infarction; Infarct size; Remote preconditioning; Preconditioning reserve; Disease; Cardiac function; Stroke work/ end diastolic lengthens; ATP; Adenosine
Abd-Elfattah AS, Guo J-H, Gao SP, Elwatidy AF, Hegab IM, Mohamad A, et al. Preconditioning of Healthy, Stunned, Infarcted, Hypertrophied and Failing Hearts: Role of Conditioning Reserve in Supplemental Cardioprotection. Clin Surg. 2019; 4: 2331..