The heart reinnervates after transplantation

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Presentation transcript:

The heart reinnervates after transplantation David A Murphy, MD, Gregory W Thompson, BSc, Jeffrey L Ardell, PhD, Rollin McCraty, Robert S Stevenson, BS, Virgilio E Sangalang, MD, René Cardinal, PhD, Michael Wilkinson, PhD, Sylvia Craig, DVM, Frank M Smith, PhD, John G Kingma, PhD, J.Andrew Armour, MD, PhD  The Annals of Thoracic Surgery  Volume 69, Issue 6, Pages 1769-1781 (June 2000) DOI: 10.1016/S0003-4975(00)01240-6

Fig 1 Holter monitor electrocardiographic data obtained from (A, B) 2 conscious animals 1 year after cardiac acute transplantation. The upper and lower panels on the left illustrate data obtained during the slowest (A, 26 bpm; B, 31 bpm) and fastest (A, 163 bpm; B, 120 bpm) heart rates in each dog. To the right are power spectral data (PSD) derived from representative 20-minute periods when bradycardia occurred in both animals. These data display similar power spectral peaks despite the fact that the heart of the dog in A exhibited no evidence of parasympathetic reinnervation, whereas that of the dog in B was reinnervated by parasympathetic efferent neurons. The Annals of Thoracic Surgery 2000 69, 1769-1781DOI: (10.1016/S0003-4975(00)01240-6)

Fig 2 Varied cardiac effects elicited in the 2 dogs in Figure 1 (A and B represent the same animals) induced by stimulating efferent axons in sectioned right (RV) or left (LV) cervical vagus individually. The times when stimuli were applied to neural tissues are indicated by the solid black sections (stimulus artifacts) recorded in the electrocardiographic traces. Note that bradycardia was elicited in 1 animal (B) but not in the other (A). (ECG = lead II electrocardiogram; LVP = left ventricular chamber pressure.) The Annals of Thoracic Surgery 2000 69, 1769-1781DOI: (10.1016/S0003-4975(00)01240-6)

Fig 3 Gross and microscopic analyses of suture lines 1 year after transplantation. (A) Gross anatomy of suture line on intimal surface of ascending aorta. (B) Masson’s trichrome stain of suture line of aorta (Ao) and pulmonary artery (PA) obtained from tissue specimen in A. (C) Neurofilament staining of same tissue demonstrating a relatively large nerve coursing over suture line to cardiac tissue at bottom of Figure. (D) Enlargement of tissue in boxed area of C. Note the deficit where a suture was located (small arrow) and axons coursing through the suture line (large arrow). Calibration bars: B and C = 10 mm; D = 2 mm. The Annals of Thoracic Surgery 2000 69, 1769-1781DOI: (10.1016/S0003-4975(00)01240-6)

Fig 4 Cardiac effects elicited by stimulating decentralized (A) left or (B) right stellate ganglion individually in animal with substantial reinnervation. Heart rate increased during right stellate ganglion stimulation, and left ventricular systolic pressure rose when either stellate ganglion was stimulated. (ECG = lead II electrocardiogram; LV IMP = left ventricular intramyocardial pressure; LVP = left ventricular chamber pressure.) The Annals of Thoracic Surgery 2000 69, 1769-1781DOI: (10.1016/S0003-4975(00)01240-6)

Fig 5 Responses displayed by two inferior vena cava–inferior right atrial neurons to intracellular or connecting nerve stimulation in vitro. (A) An action potential (upper trace) was generated by a depolarizing current pulse (1-ms duration) (lower trace) delivered into a neuron by way of the intracellular recording electrode. (B) A synaptically generated action potential occurred in the same neuron after stimulating a nerve (arrow stim) connected to the ganglion containing the identified neuron (arrow) before (Pre Hex) but not after (Hex) hexamethonium administration. Vertical bars: A = 10 mV; B = 20 mV; horizontal bars: A and B = 10 ms. The Annals of Thoracic Surgery 2000 69, 1769-1781DOI: (10.1016/S0003-4975(00)01240-6)

Fig 6 Saturable specific binding of [3H]CGP12177 to tissues (2 mm in diameter, 350 μm thick) obtained from left ventricles of control (○) and transplanted (•) hearts. Combined data derived from the ventricles of 4 study dogs and 3 control dogs are shown. The Annals of Thoracic Surgery 2000 69, 1769-1781DOI: (10.1016/S0003-4975(00)01240-6)

Fig 7 (A) Northern blot analysis was performed using specific complementary DNA probes; 18S ribosomal RNA was used as an internal control. Expression levels of messenger RNA for both α-tubulin (α-Tub) and β-tubulin (β-Tub) were augmented in myocardial tissues obtained from two transplanted hearts (T4, T6) compared with levels in control heart tissue (C). Myocardial tissue mRNA was substantially degraded in tissues obtained from a third animal (ie, T3; blot not shown). (B) Immunoblot analysis of tissue from the same myocardium demonstrating either a substantial decrease (ie, T3, T4) or no change (ie, T6) in total tubulin levels compared with control myocardial tissue. Myosin heavy chain (MHC) from a corresponding Coomassie blue–stained gel is also shown. The Annals of Thoracic Surgery 2000 69, 1769-1781DOI: (10.1016/S0003-4975(00)01240-6)