GRADIENTE TRANSCARDIACO DI NGF

Nell'unica ricerca, oltre la nostra, in cui il gradiente transcardiaco di NGF è stato stimato dalle concentrazioni in aorta ed in seno coronarico, i livelli di questo fattore di crescita risultavano essere, in tutti i soggetti considerati, superiori in seno rispetto a quelli in arteria (Kaye DM et al, 2000). Il rilievo di un gradiente medio negativo in uno studio pubblicato nel 2006 (Kangavari S et al, 2006) deve essere preso in relativa considerazione, dal momento che le concentrazioni arteriose erano stimate in arteria femorale e potevano essere alterate, quindi, da tutta una serie di variabili, prima fra tutte la produzione monocitaria di NGF. Nel nostro studio abbiamo osservato che la metà dei pazienti reclutati presentava una concentrazione arteriosa di NGF superiore a quella in seno coronarico. Nel tentativo di dare una spiegazione alle due differenti modalità di handling di NGF a livello cardiaco, abbiamo analizzato separatamente i due gruppi relativamente alle caratteristiche cliniche, ecocardiografiche, strumentali ed autonomiche. Nonostante non sia stata osservata alcuna differenza statisticamente significativa, è possibile notare un trend dei pazienti con gradiente positivo verso una sintomatologia più lieve (NYHA I-II 7, III-IV 0 vs I-II 4, III-IV 3), una migliore performance sistolica ventricolare sinistra (EF 29% vs 25%), una diametria e massa del ventricolo sinistro meglio conservata (diametro telediastolico 55 vs 58 mm; diametro telediastolico 62 vs 68 mm; LVMI 131 vs 164 g/m2

). Questi dati, pur con le opportune riserve, sono coerenti con l'ipotesi che NGF, migliorando la qualità della trasmissione sinaptica, possa, innescando un meccanismo di compenso al danno subito dall'organo bersaglio, facilitare un miglior compenso emodinamico e limitare il grado di progressione dello scompenso cardiaco e del remodeling ventricolare.

6. CONCLUSIONI

I risultati del nostro lavoro, lasciano presagire un ruolo di NGF nella disfunzione autonomica nello scompenso cardiaco, che deve essere confermato attraverso un congruo aumento della popolazione, tuttora in atto. Rimane da chiarire anche sulla base di alcune nostre osservazioni preliminari se NGF interviene nell'accoppiamento sinaptico dei soli neuroni simpatici o, come è verosimile, agisce anche su quelli parasimpatici. E' necessario, inoltre, stabilire se l'azione di NGF sul controllo nervoso della funzione cardiocircolatoria corrisponde, in effetti, ad un miglioramento della condizione del paziente, nei parametri clinici, bioumorali e strumentali.

Il raggiungimento di questi obiettivi non può prescindere dal chiarimento della biologia e della fisiologia di NGF, dalla standardizzazione delle metodiche di dosaggio e, quindi, da una più accurata definizione dei valori di riferimento delle sue concentrazioni. Solo in questo modo sarà possibile prospettare per NGF un futuro come target terapeutico emergente nel trattamento dello scompenso cardiaco.

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