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Chapter 4 Structural myocardial alterations
The first 5 sheep that were used in chapter 2 to study the normal ovine electrocardiogram were used to study the normal histological appearance of the Dorper sheep heart.
These sheep were slaughtered and the hearts removed.
Left ventricular dissection
CARDIAC MEMORY T WAVE FREQUENCY AS AN ELECTROCARDIOGRAPHIC SURROGATE FOR STRUCTURAL MYOCARDIAL ALTERATION IN THE HEARTS OF DORPER SHEEP The musculature of each left ventricle (LV) was dissected into three regions: Two transverse incisions were made, one at the level of the base and the other at the level of the apex of the posteromedial papillary muscle (see figure 4.1). This divides the LV into three regions: base, mid-region and apex. Each of these three regions were then dissected into four parts: anterior, posterior, septal and lateral. In this way every LV was dissected into 12 pieces, representing the musculature of the entire LV, which were subsequently all subjected to histological examination.
These 12 segments were numbered as follow:
A = anterior part of base
B = anterior part of mid-region
C = anterior part of apex
D = septal part of base
E = septal part of mid-region
F = septal part of apex
G = lateral part of base
H = lateral part of mid-region
I = lateral part of apex
J = posterior part of base
K = posterior part of mid-region
L = posterior part of apex
Histological evaluation
Tissue blocks from these 12 sites were fixed in 10 % buffered formalin and paraffin-embedded sections for light microscopy were prepared using routine histological procedures. They were stained with hematoxylin and eosin (HE). All the sections were then histologically examined.
Myocardial histological appearance of the normal Dorper sheep heart.
All 12 sections from the left ventricles of all 5 normal wethers had the same normal histological appearance (see figures 4.2 to 4.6).
6 of the 10 wethers that were exposed to prolonged periods of PVC`s were subsequently slaughtered and their hearts were also subjected to histological examination in order to determine if any histological differences exist between the two groups. This was done because of the peculiar finding that the morphology of PVC`s differed between the first and last day of study, findings consistent with possible myocardial pathology, as discussed in chaper Six of these 10 wethers were chosen at random for histological evaluation, the reason for excluding 4 wethers were because of financial constraints. The 6 chosen wethers were: sheep number 2, 4, 6, 7, 9 and When compared to the 5 histological control animals (see figures 4.2 to 4.6) histological changes occurred in all 6 experimental animals. These changes consisted of both myocardial cellular and interstitial abnormalities (see figures 4.7 to 4.12). According to the Dallas criteria 1, 2, 3, 4 these observed myocardial cellular and interstitial changes are indicative of myocarditis.
It has thus been shown clearly that in Dorper sheep exposed to prolonged periods of PVC`s, induced by a guidewire situated in the right ventricle, certain morphological changes appeared in these PVC`s, which are indicative of myocardial pathology. As discussed in chapter 3, these changes consist of a prolongation of the QRS complex of PVC`s, the appearance of notching of PVC`s and the disappearance of the ST segment of PVC`s. Every wether served as it`s own control at the beginning of the study when normal wethers entered the study, the PVC`s had different characteristics than at the end of the study when myocardial pathology was present. This association does not at any stage take the cause of myocardial pathology into account: we are looking at electrocardiographic surrogates of myocardial pathology and thus far, three morphological changes of PVC`s have been found as valid surrogates. The possible causes of myocardial pathology in these sheep will be discussed in chapter 6. Now, we will look if any characteristics of cardiac memory T waves can serve as an electrocardiographic surrogate for myocardial pathology.
Cardiac memory T wave frequency in the normal and diseased Dorper sheep heart.
Memory is a property common to a diverse range of tissues, such as the brain, the gastrointestinal tract and the immune system 1, 2, but is it possible for the heart to remember ? Indeed, this appears to be the case—cardiac memory has been demonstrated in the heart of the human, dog, cat and rabbit 3, 4, 5, 6.
Cardiac memory is an electrocardiographic phenomenon seen in the T wave, when T waves of normally conducted beats seem to “remember” the polarity of the QRS complexes of previous abnormally conducted beats 1, 3. Only one event is remembered by the heart and that is a period (or periods) of altered ventricular activation 1, 3, 4, 6. A variety of clinical scenarios are able to cause abnormal ventricular activation and these include: ventricular pacing, left bundle branch block, ventricular preexcitation and premature ventricular complexes 3, 4, 7, 8, 9, 10.
Rosenbaum and Blanco 3 , in their original description of cardiac memory, noted a specific sequence in cardiac memory. Periods of abnormal ventricular activation (leading to an altered sequence of ventricular depolarization) may induce a change in the T wave, which will be noted after return to a normal sequence of ventricular activation. The T wave will retain the vector of the previous abnormal QRS complex—the polarity or direction of this T wave will be the same as that of the abnormal QRS complex(es).
Cardiac memory has never before been documented in the ovine heart. The objective of this study was therefore to examine the possibility that cardiac memory can be induced and documented in the hearts of normal Dorper wethers.
Materials and methods
The 10 clinically normal Dorper wethers that were used in chapter 3 were used in this study.
These 10 wethers were exposed to right ventricular PVC’s for variable periods, as described in chapter 3 (table 5.1). The objective was to determine whether right ventricular PVC’s are able to induce cardiac memory T waves. The second objective was to see if there is any difference in the frequency of cardiac memory T waves at the beginning and end of the study period.
Results
A total of 5359 PVC’s were counted and documented on a 12-lead surface electrocardiogram. In order to detect if there is any difference between the early and late occurrence of cardiac memory T waves the first and last 10 % of PVC’s were evaluated in every wether. The T wave of the first normal beat after every PVC were evaluated in order to determine whether these T waves retained the vector of the previous PVC QRS complex (table 5.2). Only lead III of the 12-lead, surface electrocardiogram were used to assess for the presence of cardiac memory T waves as a pilot study showed that this is the lead with the highest yield for cardiac memory T waves
Discussion
This is the first report of cardiac memory in sheep 11. Cardiac memory T waves may appear after either short or long periods of altered ventricular activation 1, 4. However, there is no consensus yet in the literature on the time period required to separate short- from long-term cardiac memory 4. Rosenbaum and Blanco 3 in the first cardiac memory experiments needed 15 minutes of right ventricular pacing to demonstrate memory T waves in the human heart. Goyal and Syed 12 were able to induce cardiac memory after only 1 minute of right ventricular pacing in humans. This study demonstrates 2 concepts: First, the ovine heart is able to manifest cardiac memory T waves, and secondly the higher the load of altered ventricular activation (PVC’s were used in this study) the more likely the manifestation of cardiac memory, as demonstrated by an odds ratio (OR) of 10.38 (the OR=10.38 that the amount of cardiac memory T waves will increase during the last 10% of PVC’s as compared to during the first 10% of PVC’s).
Currently, it is not known whether cardiac memory T waves can serve as an electrocardiographic warning for future myocardial pathology. In this study, it was shown that the true value of using cardiac memory T waves as an electrocardiographic surrogate for structural myocardial alteration in the Dorper sheep heart does not lie in an instantaneous electrocardiographic assessment, but in electrocardiographic follow-up in order to determine if there is an increase in the frequency of cardiac memory T waves. As shown in this study an increase of at least 42 % in the frequency of cardiac memory T waves, following PVC`s is indicative of underlying structural myocardial changes in the Dorper sheep heart.
Chapter 1 Introduction
– Electrocardiography of the normal T wave
– Conditions associated with T wave changes that cannot be explained by Wilson`s formulation
– Cardiac memory
– Conditions associated with cardiac memory T waves that
may cause myocardial disease
– Hypothesis
– Research needed
– References
Chapter 2 The normal ovine electrocardiogram: A 12-leaded approach
Chapter 3 The morphology of premature ventricular complexes in the Dorper sheep heart
Chapter 4 Structural myocardial alterations
Chapter 5 Cardiac memory T wave frequency in the normal and diseased Dorper sheep heart
Chapter 6 Summary
Addendum
Abbreviations
List of figures and tables
Acknowledgements
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