Neuroleptic Cardiomyopathy and Myocardial Hibernation

Aim: It is to summarize and in a new way to interpret the data, which have been earlier received, in order to prove the development of the hibernation of myocardium (HM) in cases of the neuroleptic cardiomyopathy (NCMP). Methods and results: Morphometric methods of research were used which meet modern requirements of the evidence-based medicine. The studied micro morphometric parameters describe the condition of three structural components of myocardium (vasculature, intercellular matrix, and parenchyma). Such parameters as zone of pericapillary diffusion (ZPD), Kernogan index (KI), SPR, RIE were calculated. Karyometry and cytometry of cardiomyocytes (CMCs) were performed, the specific volumes of hypertrophied CMCs (SVHC), of atrophied ones (SVAC), and – by the method of polarization microscopy – the specific volume of dystrophic ones (SVDC) were determined. When NCMP is absent, the changes, which have an acute character, develop in the case of SCD and NMS and reflect the statistically significant shifts of the respective quantitative parameters. When NCMP is present, the only parameter, which is significantly changed in connection with SCD and NMS, is SVDC. Conclusion: NCMP causes irreversible damages in myocardium, it leads to its are activity, practically almost fully prevents it from reacting to any influences, particularly to the coming of SCD and/or development of NMS. The found morpho functional state of cardiac muscle in the case of NCMP is an independent proof of state of HM which appears during the process of morphogenesis of NCMP.


Introduction
The term "hibernating (dormant) myocardium" is used to describe a distinctive state of cardiac muscle in conditions of its long ischemia [1][2][3][4]. When the hibernation of myocardium (HM) is present, the metabolic energy processes in cardiomyocytes (CMC's) are minimized, the contractility of the latter's is reduced but their viability is preserved [3,5]. HM is often observed when different forms of coronary heart disease (CHD) [1,3,6,7] including the ischemic cardiomyopathy (ICMP) [6] are present, and in cases of development of chronic heart failure (CHF) [1]. It seems that HM can be considered as a general pathologic adaptive process which develops in the myocardium when its ischemia of any genesis is present [2][3][4][5]7].
Reports about HM in cases of cardiomyopathies, a diabetic cardiomyopathy [8] and idiopathic dilated one (DCMP) [9] indeed appeared recently. However, there are no reports about HM in cases of neuroleptic cardiomyopathy (NCMP) in literature although NCMP belongs to specific (secondary) DCMP's [10] as well as ICMP, but HM is quite often observed in cases of ICMP [6]. It should be said that the clinical course of both diseases [11,12], their path morphology [13] and pathogenesis, which is based on myocardial ischemia, have much in common [14,15]. We conducted our own morphologic study of heart after sudden cardiac death (SCD) had occurred in patients with NCMP or malignant neuroleptic syndrome (NMS) had developed in them and we found that myocardium gets a certain are activity in cases of NCMP and does not react to such acute stress situations as SCD and NMS [16][17][18]. It leads to a natural question whether such are activity is a sign of presence of HM.
Therefore, the aim of the present study is to summarize and in a

Materials and Methods
Myocardium of 169 dead persons was studied who had schizophrenia (men -105, women -64; age -from 16 to 77 years) and over the period from a half-year to 30 and more years

Results
When NCMP is absent, the changes, which have an acute

Discussion
Myocardium morphology of the patients, who received AD but hadn't NCMP, is strongly affected both by SCD and NMS [13,16,17,20,21]. which later on become less important [13,14], deprive myocardium micro vessels of the level of reactivity which is inherent in them.
Parameters of state of extracellular matrix (stroma) of myocardium haven't any significant negative changes too. The statistically significant difference of SPR, which is discovered in the case of NMS in the compared groups V и VII, is evidence of a less apparent process of sclerosis of myocardium stroma in the case of comorbid pathology; this difference has no pathogenetic significance for development of myocardial injuries in the case of NMS for the following reasons.
It is known that young and middle-aged persons (from 20 to 40 years) are more often affected in the case of NMS [18,24].
Therefore, the group VII mainly includes patients in whom NCMP Myofibrosis is yet relatively moderately apparent in these stages of the disease morphogenesis [13,14]. On the contrary, the group V includes patients with NCMP whose stage is not taken into consideration, many of them died of CHF in the terminal stage of the disease when the development of my fibrosis is maximally apparent. The above-mentioned circumstances also explain the decrease of SVAC which is found in cases of comorbid course of NMS and NCMP. The only parameter of the studied ones, which responds to development of such fatal situations as SCD and NMS, is SVDC. Its growth in both cases reflect processes of severe damage of CMC's and these processes inevitably progress in the cases of SCD and/or NMS, even in the presence of NCMP.
Thus, the quantitative structural parameters of myocardium, whose changes take rather much time (SPR, SVHC and SVAC) -and exactly it is observed in the process of morphogenesis of NCMP [13,14] -remain without any significant changes when SCD occurs and/or NMS develops. At the same time, it is important to emphasize that such acutely developing pathologic processes as disturbances of microcirculation and progression of interstitial edema are not apparent in the cases of SCD and/or NMS in combination with NCMP either. It follows from what has been said that NCMP causes irreversible damages in myocardium, it leads to its are activity, practically almost fully prevents it from reacting to any influences, particularly to the coming of SCD and/or development of NMS.
The found morpho functional state of cardiac muscle in the case of NCMP is analogous to HM which has been described in cases of ICMP [1][2][3]6,7].

Conclusion
The conducted morphometric study of changes of myocardium at the coming of SCD and/or development of NMS in patients without NCMP on the one hand, and in the presence of the mentioned iatrogenic pathology on the other hand, has discovered significant differences. When NCMP is present, a considerable decrease of reactivity of all studied structural components of cardiac muscle is observed, i.e. microvasculature, extracellular matrix and CMC's. This fact is an independent proof of state of HM which appears during the process of morphogenesis of NCMP what has not been so far described in literature.